Evaluación del efecto de hipoxia en la expresión de canales TRP y sus miRNAs asociados en leucocitos aislados de sangre periférica

Resumen: Los canales iónicos son proteínas de membrana que se expresan tanto en células excitables como no excitables, en donde cumplen diferentes funciones biológicas incluyendo proliferación, diferenciación, migración y apoptosis. Diversos canales iónicos participan en la regulación de la fisiología cardiovascular, incluyendo canales de la familia de los TRP. Por ejemplo, los TRPC6 son canales mecanosensibles que participan en la regulación del tono vascular través de un mecanismo que involucra las vías fosfolipasa C/diacilglicerol y fosfolipasa A2/20-HETE ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1152/ajpheart.00457.2014","ISSN":"15221539","abstract":" The transient receptor potential (TRP) superfamily consists of a large number of nonselective cation channels with variable degree of Ca 2+ -permeability. The 28 mammalian TRP channel proteins can be grouped into six subfamilies: canonical, vanilloid, melastatin, ankyrin, polycystic, and mucolipin TRPs. The majority of these TRP channels are expressed in different cell types including both excitable and nonexcitable cells of the cardiovascular system. Unlike voltage-gated ion channels, TRP channels do not have a typical voltage sensor, but instead can sense a variety of other stimuli including pressure, shear stress, mechanical stretch, oxidative stress, lipid environment alterations, hypertrophic signals, and inflammation products. By integrating multiple stimuli and transducing their activity to downstream cellular signal pathways via Ca 2+ entry and/or membrane depolarization, TRP channels play an essential role in regulating fundamental cell functions such as contraction, relaxation, proliferation, differentiation, and cell death. With the use of targeted deletion and transgenic mouse models, recent studies have revealed that TRP channels are involved in numerous cellular functions and play an important role in the pathophysiology of many diseases in the cardiovascular system. Moreover, several TRP channels are involved in inherited diseases of the cardiovascular system. This review presents an overview of current knowledge concerning the physiological functions of TRP channels in the cardiovascular system and their contributions to cardiovascular diseases. Ultimately, TRP channels may become potential therapeutic targets for cardiovascular diseases. ","author":[{"dropping-particle":"","family":"Yue","given":"Zhichao","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Xie","given":"Jia","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yu","given":"Albert S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Stock","given":"Jonathan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Du","given":"Jianyang","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yue","given":"Lixia","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"American Journal of Physiology - Heart and Circulatory Physiology","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2015"]]},"page":"H157-H182","title":"Role of trp channels in the cardiovascular system","type":"article-journal","volume":"308"},"uris":["http://www.mendeley.com/documents/?uuid=a002b49f-d40d-4b44-b778-51b6e9bc9180"]}],"mendeley":{"formattedCitation":"(Yue et al., 2015)","plainTextFormattedCitation":"(Yue et al., 2015)","previouslyFormattedCitation":"(Yue et al., 2015)"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(Yue et al., 2015). Por su parte, canales TRPC1 se expresan en músculo liso vascular y participan en la regulación de la vasoconstricción y de la proliferación ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"abstract":"1. ABSTRACT Transient receptor potential canonical (TRPC) proteins constitute a family of seven (TRPC1-7) nonselective cation channels within the wider TRP superfamily. TRPC1, TRPC3, TRPC4, TRPC5 and TRPC6 channels are expressed in vascular smooth muscle cells from human vessels of all calibers and in smooth muscle from organs such as the uterus and the gastrointestinal tract. TRPC channels have recently emerged as important players in the control of smooth muscle function. This review will focus on the retrospective analysis of studies proposing contributions of TRPC channels to native calcium entry pathways in smooth muscle and to physiological and pathophysiological responses with emphasis on the vascular system. Calcium (Ca 2+) ions impact nearly every aspect of cellular life and are considered universal intracellular messengers controlling a diverse range of cellular processes, including skeletal, cardiac and smooth muscle contraction, neuronal growth and neurotransmitter release [1; 2; 3]. The spatial localization of Ca 2+ signals also contribute to increase the diversity of signals that can be successfully transmitted to downstream effectors [4]. Vascular smooth muscle cells (SMCs) form a layer of contractile cells in the blood vessel wall and are known to be instrumental in maintaining the blood vessel structural integrity and regulating blood pressure and blood flow distribution [5; 6; 7]. It is by the coordinated contraction and relaxation of these cells that the blood vessel diameter and stiffness can be modulated, thereby serving as one of the principal clinical control points for cardiovascular physiological parameters. In vascular SMCs, Ca 2+ signals have been suggested as modulators of cellular functions such as gene transcription, cell proliferation, contraction and phenotypic modulation that occur during vascular disease [5; 8; 9]. Cytosolic Ca 2+ levels are carefully maintained at the hundred nanomolar range and Ca 2+ signals can be generated through Ca 2+ mobilization from either the intracellular stores (mainly the sarcoplasmic reticulum; SR) or the extracellular space. By means of Ca 2+ permeable channels and Ca 2+ pumps that mediate Ca 2+ entry and Ca 2+ extrusion/buffering respectively, SMCs keep intracellular Ca 2+ levels under tight control. The vascular tone or contractile state of the vessels is regulated through changes in the membrane potential of SMCs whereby membrane depolarization activates Ca 2+ entry through voltage-act…","author":[{"dropping-particle":"","family":"González-Cobos","given":"José C","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Trebak","given":"Mohamed","non-dropping-particle":"","parse-names":false,"suffix":""}],"id":"ITEM-1","issue":"518","issued":{"date-parts":[["2011"]]},"page":"1023-1039","title":"TRPC channels in smooth muscle cells 2. CALCIUM SIGNALING IN SMOOTH MUSCLE CELLS","type":"article-journal"},"uris":["http://www.mendeley.com/documents/?uuid=c85e55c9-2be0-4c78-b864-6e33e7bec0e7"]}],"mendeley":{"formattedCitation":"(González-Cobos & Trebak, 2011)","plainTextFormattedCitation":"(González-Cobos & Trebak, 2011)","previouslyFormattedCitation":"(González-Cobos & Trebak, 2011)"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(González-Cobos & Trebak, 2011). En arteria pulmonar de rata se observó que la sobreexpresión de TRPC1 induce la entrada de calcio y promueve la contracción, al igual que la hipertensión asociada a la hipoxia ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1152/ajpheart.00457.2014","ISSN":"15221539","abstract":" The transient receptor potential (TRP) superfamily consists of a large number of nonselective cation channels with variable degree of Ca 2+ -permeability. The 28 mammalian TRP channel proteins can be grouped into six subfamilies: canonical, vanilloid, melastatin, ankyrin, polycystic, and mucolipin TRPs. The majority of these TRP channels are expressed in different cell types including both excitable and nonexcitable cells of the cardiovascular system. Unlike voltage-gated ion channels, TRP channels do not have a typical voltage sensor, but instead can sense a variety of other stimuli including pressure, shear stress, mechanical stretch, oxidative stress, lipid environment alterations, hypertrophic signals, and inflammation products. By integrating multiple stimuli and transducing their activity to downstream cellular signal pathways via Ca 2+ entry and/or membrane depolarization, TRP channels play an essential role in regulating fundamental cell functions such as contraction, relaxation, proliferation, differentiation, and cell death. With the use of targeted deletion and transgenic mouse models, recent studies have revealed that TRP channels are involved in numerous cellular functions and play an important role in the pathophysiology of many diseases in the cardiovascular system. Moreover, several TRP channels are involved in inherited diseases of the cardiovascular system. This review presents an overview of current knowledge concerning the physiological functions of TRP channels in the cardiovascular system and their contributions to cardiovascular diseases. Ultimately, TRP channels may become potential therapeutic targets for cardiovascular diseases. ","author":[{"dropping-particle":"","family":"Yue","given":"Zhichao","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Xie","given":"Jia","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yu","given":"Albert S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Stock","given":"Jonathan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Du","given":"Jianyang","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yue","given":"Lixia","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"American Journal of Physiology - Heart and Circulatory Physiology","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2015"]]},"page":"H157-H182","title":"Role of trp channels in the cardiovascular system","type":"article-journal","volume":"308"},"uris":["http://www.mendeley.com/documents/?uuid=a002b49f-d40d-4b44-b778-51b6e9bc9180"]}],"mendeley":{"formattedCitation":"(Yue et al., 2015)","plainTextFormattedCitation":"(Yue et al., 2015)","previouslyFormattedCitation":"(Yue et al., 2015)"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(Yue et al., 2015) ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"abstract":"1. ABSTRACT Transient receptor potential canonical (TRPC) proteins constitute a family of seven (TRPC1-7) nonselective cation channels within the wider TRP superfamily. TRPC1, TRPC3, TRPC4, TRPC5 and TRPC6 channels are expressed in vascular smooth muscle cells from human vessels of all calibers and in smooth muscle from organs such as the uterus and the gastrointestinal tract. TRPC channels have recently emerged as important players in the control of smooth muscle function. This review will focus on the retrospective analysis of studies proposing contributions of TRPC channels to native calcium entry pathways in smooth muscle and to physiological and pathophysiological responses with emphasis on the vascular system. Calcium (Ca 2+) ions impact nearly every aspect of cellular life and are considered universal intracellular messengers controlling a diverse range of cellular processes, including skeletal, cardiac and smooth muscle contraction, neuronal growth and neurotransmitter release [1; 2; 3]. The spatial localization of Ca 2+ signals also contribute to increase the diversity of signals that can be successfully transmitted to downstream effectors [4]. Vascular smooth muscle cells (SMCs) form a layer of contractile cells in the blood vessel wall and are known to be instrumental in maintaining the blood vessel structural integrity and regulating blood pressure and blood flow distribution [5; 6; 7]. It is by the coordinated contraction and relaxation of these cells that the blood vessel diameter and stiffness can be modulated, thereby serving as one of the principal clinical control points for cardiovascular physiological parameters. In vascular SMCs, Ca 2+ signals have been suggested as modulators of cellular functions such as gene transcription, cell proliferation, contraction and phenotypic modulation that occur during vascular disease [5; 8; 9]. Cytosolic Ca 2+ levels are carefully maintained at the hundred nanomolar range and Ca 2+ signals can be generated through Ca 2+ mobilization from either the intracellular stores (mainly the sarcoplasmic reticulum; SR) or the extracellular space. By means of Ca 2+ permeable channels and Ca 2+ pumps that mediate Ca 2+ entry and Ca 2+ extrusion/buffering respectively, SMCs keep intracellular Ca 2+ levels under tight control. The vascular tone or contractile state of the vessels is regulated through changes in the membrane potential of SMCs whereby membrane depolarization activates Ca 2+ entry through voltage-act…","author":[{"dropping-particle":"","family":"González-Cobos","given":"José C","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Trebak","given":"Mohamed","non-dropping-particle":"","parse-names":false,"suffix":""}],"id":"ITEM-1","issue":"518","issued":{"date-parts":[["2011"]]},"page":"1023-1039","title":"TRPC channels in smooth muscle cells 2. CALCIUM SIGNALING IN SMOOTH MUSCLE CELLS","type":"article-journal"},"uris":["http://www.mendeley.com/documents/?uuid=c85e55c9-2be0-4c78-b864-6e33e7bec0e7"]}],"mendeley":{"formattedCitation":"(González-Cobos & Trebak, 2011)","plainTextFormattedCitation":"(González-Cobos & Trebak, 2011)","previouslyFormattedCitation":"(González-Cobos & Trebak, 2011)"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(González-Cobos & Trebak, 2011). Finalmente, canales TRPV4 participan directamente en la regulación del tono vascular y su función involucra la activación de canales de potasio dependientes de calcio de alta (BKCa)ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1152/ajpheart.00457.2014","ISSN":"15221539","abstract":" The transient receptor potential (TRP) superfamily consists of a large number of nonselective cation channels with variable degree of Ca 2+ -permeability. The 28 mammalian TRP channel proteins can be grouped into six subfamilies: canonical, vanilloid, melastatin, ankyrin, polycystic, and mucolipin TRPs. The majority of these TRP channels are expressed in different cell types including both excitable and nonexcitable cells of the cardiovascular system. Unlike voltage-gated ion channels, TRP channels do not have a typical voltage sensor, but instead can sense a variety of other stimuli including pressure, shear stress, mechanical stretch, oxidative stress, lipid environment alterations, hypertrophic signals, and inflammation products. By integrating multiple stimuli and transducing their activity to downstream cellular signal pathways via Ca 2+ entry and/or membrane depolarization, TRP channels play an essential role in regulating fundamental cell functions such as contraction, relaxation, proliferation, differentiation, and cell death. With the use of targeted deletion and transgenic mouse models, recent studies have revealed that TRP channels are involved in numerous cellular functions and play an important role in the pathophysiology of many diseases in the cardiovascular system. Moreover, several TRP channels are involved in inherited diseases of the cardiovascular system. This review presents an overview of current knowledge concerning the physiological functions of TRP channels in the cardiovascular system and their contributions to cardiovascular diseases. Ultimately, TRP channels may become potential therapeutic targets for cardiovascular diseases. ","author":[{"dropping-particle":"","family":"Yue","given":"Zhichao","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Xie","given":"Jia","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yu","given":"Albert S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Stock","given":"Jonathan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Du","given":"Jianyang","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yue","given":"Lixia","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"American Journal of Physiology - Heart and Circulatory Physiology","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2015"]]},"page":"H157-H182","title":"Role of trp channels in the cardiovascular system","type":"article-journal","volume":"308"},"uris":["http://www.mendeley.com/documents/?uuid=a002b49f-d40d-4b44-b778-51b6e9bc9180"]}],"mendeley":{"formattedCitation":"(Yue et al., 2015)","plainTextFormattedCitation":"(Yue et al., 2015)","previouslyFormattedCitation":"(Yue et al., 2015)"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(Yue et al., 2015) y de pequeña conductancia (SKCa) ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1161/HYPERTENSIONAHA.116.07110","ISSN":"15244563","abstract":"© 2016 American Heart Association, Inc. Endothelium-dependent hyperpolarization (EDH)-mediated responses are impaired in hypertension, but the underlying mechanisms have not yet been determined. The activation of small- and intermediate-conductance of Ca 2+ -activated K + channels (SK Ca and IK Ca) underpins EDH-mediated responses. It was recently reported that Ca 2+ influx through endothelial transient receptor potential vanilloid type 4 channel (TRPV4) is a prerequisite for the activation of SK Ca /IK Ca in endothelial cells in specific beds. Here, we attempted to determine whether the impairment of EDH in hypertension is attributable to the dysfunction of TRPV4 and S/IK Ca, using isolated superior mesenteric arteries of 20-week-old stroke-prone spontaneously hypertensive rats (SHRSP) and age-matched Wistar-Kyoto (WKY) rats. In the WKY arteries, EDH-mediated responses were reduced by a combination of SK Ca /IK Ca blockers (apamin plus TRAM-34; 1-[(2-chlorophenyl)diphenylmethl]-1H-pyrazole) and by the blockade of TRPV4 with the selective antagonist RN-1734 or HC-067047. In the SHRSP arteries, EDH-mediated hyperpolarization and relaxation were significantly impaired when compared with WKY. GSK1016790A, a selective TRPV4 activator, evoked robust hyperpolarization and relaxation in WKY arteries. In contrast, in SHRSP arteries, the GSK1016790A-evoked hyperpolarization was small and relaxation was absent. Hyperpolarization and relaxation to cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine, a selective SK Ca activator, were marginally decreased in SHRSP arteries compared with WKY arteries. The expression of endothelial TRPV4 and SK Ca protein was significantly decreased in the SHRSP mesenteric arteries compared with those of WKY, whereas function and expression of IK Ca were preserved in SHRSP arteries. These findings suggest that EDH-mediated responses are impaired in superior mesenteric arteries of SHRSP because of a reduction in both TRPV4 and SK Ca input to EDH.","author":[{"dropping-particle":"","family":"Seki","given":"Takunori","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Goto","given":"Kenichi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kiyohara","given":"Kanako","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kansui","given":"Yasuo","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Murakami","given":"Noboru","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Haga","given":"Yoshie","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ohtsubo","given":"Toshio","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Matsumura","given":"Kiyoshi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kitazono","given":"Takanari","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Hypertension","id":"ITEM-1","issue":"1","issued":{"date-parts":[["2017"]]},"page":"143-153","title":"Downregulation of Endothelial Transient Receptor Potential Vanilloid Type 4 Channel and Small-Conductance of Ca 2+ -Activated K + Channels Underpins Impaired Endothelium-Dependent Hyperpolarization in Hypertension","type":"article-journal","volume":"69"},"uris":["http://www.mendeley.com/documents/?uuid=047fb8a6-5ba4-4925-895a-03673510098a"]}],"mendeley":{"formattedCitation":"(Seki et al., 2017)","plainTextFormattedCitation":"(Seki et al., 2017)","previouslyFormattedCitation":"(Seki et al., 2017)"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(Seki et al., 2017). El mecanismo implica la formación de un complejo con receptores de rianodina (RyRs) que genera un incremento en la frecuencia de las chispas de calcio, lo que a su vez activa canales BKCa e induce hiperpolarización y vasorelajación ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1152/ajpheart.00457.2014","ISSN":"15221539","abstract":" The transient receptor potential (TRP) superfamily consists of a large number of nonselective cation channels with variable degree of Ca 2+ -permeability. The 28 mammalian TRP channel proteins can be grouped into six subfamilies: canonical, vanilloid, melastatin, ankyrin, polycystic, and mucolipin TRPs. The majority of these TRP channels are expressed in different cell types including both excitable and nonexcitable cells of the cardiovascular system. Unlike voltage-gated ion channels, TRP channels do not have a typical voltage sensor, but instead can sense a variety of other stimuli including pressure, shear stress, mechanical stretch, oxidative stress, lipid environment alterations, hypertrophic signals, and inflammation products. By integrating multiple stimuli and transducing their activity to downstream cellular signal pathways via Ca 2+ entry and/or membrane depolarization, TRP channels play an essential role in regulating fundamental cell functions such as contraction, relaxation, proliferation, differentiation, and cell death. With the use of targeted deletion and transgenic mouse models, recent studies have revealed that TRP channels are involved in numerous cellular functions and play an important role in the pathophysiology of many diseases in the cardiovascular system. Moreover, several TRP channels are involved in inherited diseases of the cardiovascular system. This review presents an overview of current knowledge concerning the physiological functions of TRP channels in the cardiovascular system and their contributions to cardiovascular diseases. Ultimately, TRP channels may become potential therapeutic targets for cardiovascular diseases. ","author":[{"dropping-particle":"","family":"Yue","given":"Zhichao","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Xie","given":"Jia","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yu","given":"Albert S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Stock","given":"Jonathan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Du","given":"Jianyang","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yue","given":"Lixia","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"American Journal of Physiology - Heart and Circulatory Physiology","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2015"]]},"page":"H157-H182","title":"Role of trp channels in the cardiovascular system","type":"article-journal","volume":"308"},"uris":["http://www.mendeley.com/documents/?uuid=a002b49f-d40d-4b44-b778-51b6e9bc9180"]}],"mendeley":{"formattedCitation":"(Yue et al., 2015)","plainTextFormattedCitation":"(Yue et al., 2015)","previouslyFormattedCitation":"(Yue et al., 2015)"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(Yue et al., 2015). La expresión y actividad de estos canales es regulada por diferentes procesos fisiológicos que pueden involucrar mecanismos epigenéticos como los microARNs (miRNA), o estímulos externos tales como la hipoxia, la cual también puede inducir cambios en la actividad de estos. La hipoxia crónica se asocia a alteraciones en la homeóstasis de calcio y hay reportes que indican que puede afectar tanto la entrada de calcio como su liberación desde depósitos intracelulares a través de la actividad de canales TRP (Peng et al., 2015). En células de músculo liso vascular y endotelio se ha encontrado que canales de la familia de TRP (por sus siglas en inglés Transient receptor potential), incluyendo TRPC1, TRPC6 y TRPV4, entre otros, incrementan su expresión después de un estímulo de hipoxia. Por tal motivo se han llevado a cabo estudios enfocados a entender el papel de estos canales en el desarrollo de enfermedades cardiovasculares. Con relación a los mecanismos de regulación epigenéticos, hay diferentes microRNAs reportados como moduladores de la expresión de canales de la familia TRP. Entre ellos, miR-122 y miR-234 regulan la expresión de TRPC1, miR-201 y miR-332 han sido reportados como reguladores de la expresión de TRCP6 y miR-75 y miR-498 están asociados con la regulación de la expresión de TRPV4. Diversos estudios reportan el uso de canales iónicos como biomarcadores de algunas patologías. Por ejemplo, la expresión de canales de cloruro activados por calcio (CLCA1) se ha sugerido como biomarcador para adenocarcinoma pancreático ductal y cáncer colorectal ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1186/s12885-018-5013-2","ISSN":"14712407","abstract":"BACKGROUND: In a previous study utilizing mass spectrometry-based proteomics, we identified calcium-activated chloride channel regulator 1 (CLCA1) as a potential tumor suppressor in pancreatic cancer and the expression was inversely correlated with patient survival. The aim of the study was to further validate the prognostic significance of CLCA1 in pancreatic cancer. METHODS: CLCA1 expression was evaluated with tissue microarrays and immunohistochemistry in 140 patients with pancreatic ductal adenocarcinoma that underwent surgical resection at Skåne University Hospital, Sweden. Kaplan-Meier and Cox proportional hazards modeling were used to explore the association between CLCA1 and clinicopathological factors and survival. RESULTS: CLCA1 expression was denoted as positive in 90 tumors (64.3%), with positive staining being limited to the tumor cells. There were no significant association between CLCA1 expression and established clinicopathological parameters. Low CLCA1 expression correlated significantly with shorter disease-free survival (11.9 vs 17.5 months, P = 0.042). Multivariable Cox regression analysis confirmed the results (HR 0.61, 95% CI-0.40-0.92, P = 0.019). CONCLUSIONS: Low CLCA1 expression is an independent factor of poor disease-free survival in pancreatic cancer.","author":[{"dropping-particle":"","family":"Hu","given":"Dingyuan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ansari","given":"Daniel","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zhou","given":"Qimin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sasor","given":"Agata","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hilmersson","given":"Katarzyna Said","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bauden","given":"Monika","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Jiang","given":"Yi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Andersson","given":"Roland","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"BMC Cancer","id":"ITEM-1","issue":"1","issued":{"date-parts":[["2018"]]},"page":"1-6","publisher":"BMC Cancer","title":"Calcium-activated chloride channel regulator 1 as a prognostic biomarker in pancreatic ductal adenocarcinoma","type":"article-journal","volume":"18"},"uris":["http://www.mendeley.com/documents/?uuid=a377f26b-9582-4806-8d21-4f61af309c14"]}],"mendeley":{"formattedCitation":"(Hu et al., 2018)","plainTextFormattedCitation":"(Hu et al., 2018)","previouslyFormattedCitation":"(Hu et al., 2018)"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(Hu et al., 2018). El canal CLIC1 se reporta como marcador diagnóstico para carcinoma escamoso oral ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.2147/OTT.S181936","ISSN":"11786930","abstract":"Purpose CLIC1, a member of the highly conserved class ion-channel protein family, is frequently upregulated in multiple human malignancies and has been demonstrated to play a critical role in cell proliferation, apoptosis, and invasion. However, limited is known about its expression, biological functions, and action mechanism in oral malignancies. We aimed to evaluate whether CLIC1 could be a biomarker for oral squamous cell carcinoma (OSCC). Methods Immunohistochemistry was used to analyze the expression of CLIC1 in tissue. CLIC1 protein and mRNA were measured through Western immunoblotting and quantitative real-time PCR. CLIC1 protein expression in plasma was detected via ELISA. A total of 72 OSCC specimens were recruited in this study for evaluation of correlations of CLIC1 with clinicopathological features and survival. Results CLIC1 was significantly overexpressed in tissue and plasma of OSCC patients. It was found that upregulated CLIC1 was distinctly correlated with histological grade, TNM stage, and tumor size. Meanwhile, Kaplan-Meier survival analysis showed that OSCC patients with high CLIC1 expression had remarkably poorer overall survival rate than those with low CLIC1 expression. Multivariate Cox regression analysis revealed that CLIC1 was the independent prognostic factor for overall survival rate of OSCC patients. In addition, Pearson correlation analysis showed that CLIC1 was associated with multiple tumor-associated genes. Conclusion These results indicated that CLIC1 acts as a molecular target in OSCC and may present a novel diagnostic marker and therapeutic target for OSCC.","author":[{"dropping-particle":"","family":"Xu","given":"Ying","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Xu","given":"Jie","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Feng","given":"Jiali","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Li","given":"Jie","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Jiang","given":"Chao","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Li","given":"Xian","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zou","given":"Sihai","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wang","given":"Qian","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Li","given":"Yong","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"OncoTargets and Therapy","id":"ITEM-1","issued":{"date-parts":[["2018"]]},"page":"8073-8081","title":"Expression of CLIC1 as a potential biomarker for oral squamous cell carcinoma: A preliminary study","type":"article-journal","volume":"11"},"uris":["http://www.mendeley.com/documents/?uuid=3ee4b7bd-46ce-43bc-82d1-50fdfa93d039"]}],"mendeley":{"formattedCitation":"(Xu et al., 2018)","plainTextFormattedCitation":"(Xu et al., 2018)","previouslyFormattedCitation":"(Xu et al., 2018)"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(Xu et al., 2018) y los canales de cloruro CIC-3 tienen incrementada sobre-expresión en carcinoma hepático y se propone como marcador de prognosis en pacientes con esta patología ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/j.acthis.2019.01.006","ISSN":"16180372","abstract":"Chloride channel 3 (CIC-3) has been suggested to be implicated in the carcinogenesis though; it still remains ill understood in hepatocarcinoma, especially in terms of clinicopathological meaning of its expression. Given this, herein, to understand the clinicopathological significance of CIC-3 expression in hepatocarcinoma, Immunohistochemistry was performed to examine the level of CIC-3, followed by statistical analysis of the correlation between expression versus clinicopathological variables, including gender, age, TNM classifications, tumor size, lymph node metastasis and overall prognosis. It was shown that positive staining of CIC-3 can be present in both hepatocarcinoma and its paired normal controls; and that CIC-3 was significantly over-expressed in hepatcarcioma on the whole relative to paired normal controls. Moreover, up-regulation of CIC-3 markedly correlated with tumor size and overall prognosis, suggesting that CIC-3 expression could predict both tumor size and overall prognosis in hepatocarcinoma.","author":[{"dropping-particle":"","family":"Cheng","given":"Wei","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zheng","given":"Shutao","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Li","given":"Li","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zhou","given":"Qin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zhu","given":"Haipeng","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hu","given":"Jun","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Luo","given":"Hongbin","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Acta Histochemica","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2019"]]},"page":"284-288","title":"Chloride channel 3 (CIC-3) predicts the tumor size in hepatocarcinoma","type":"article-journal","volume":"121"},"uris":["http://www.mendeley.com/documents/?uuid=1f0a826b-b122-462e-9700-99ce59e3b06a"]}],"mendeley":{"formattedCitation":"(Cheng et al., 2019)","plainTextFormattedCitation":"(Cheng et al., 2019)","previouslyFormattedCitation":"(Cheng et al., 2019)"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(Cheng et al., 2019). Dentro de la familia de los canales TRP, se ha evidenciado una significativa sobre-expresión de canales TRPM8 en cáncer de mama, de próstata y en adenocarcinoma pancreático, por lo cual este canal se ha estudiado como biomarcador para diagnóstico temprano, prognosis y monitoreo de la respuesta terapéutica ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/j.molmed.2012.11.004","ISSN":"14714914","abstract":"Breast cancer is the most frequently occurring cancer in women and has the highest rate of mortality. Ion channels such as the transient receptor potential (TRP) channels could play a critical role in the development and progression of cancer. Although these channels are frequently and abundantly expressed in many tumors, their expression, activity, and roles in the context of breast cancer remain poorly understood. This review summarizes our current knowledge regarding TRP channels expressed in human breast tissue, primary human breast epithelial cells, and cell lines, the functional role of TRP channels during breast cancer cell growth and migration, as well as their relationship with clinical and pathological features. © 2012 Elsevier Ltd.","author":[{"dropping-particle":"","family":"Ouadid-Ahidouch","given":"Halima","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Dhennin-Duthille","given":"Isabelle","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gautier","given":"Mathieu","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sevestre","given":"Henri","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ahidouch","given":"Ahmed","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Trends in Molecular Medicine","id":"ITEM-1","issue":"2","issued":{"date-parts":[["2013"]]},"page":"117-124","publisher":"Elsevier Ltd","title":"TRP channels: Diagnostic markers and therapeutic targets for breast cancer?","type":"article-journal","volume":"19"},"uris":["http://www.mendeley.com/documents/?uuid=7a28e98d-e891-49fb-aabd-1dc548b655f5"]}],"mendeley":{"formattedCitation":"(Ouadid-Ahidouch, Dhennin-Duthille, Gautier, Sevestre, & Ahidouch, 2013)","plainTextFormattedCitation":"(Ouadid-Ahidouch, Dhennin-Duthille, Gautier, Sevestre, & Ahidouch, 2013)","previouslyFormattedCitation":"(Ouadid-Ahidouch, Dhennin-Duthille, Gautier, Sevestre, & Ahidouch, 2013)"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(Ouadid-Ahidouch, Dhennin-Duthille, Gautier, Sevestre, & Ahidouch, 2013). Los canales TRPV2 y TRPV4 se sugieren como biomarcadores de prognosis de melanoma humano, en donde su inhibición farmacológica disminuyó la proliferación celular ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1155/2019/7362875","ISSN":"16878469","abstract":" Background . Thermo-TRPs (temperature-sensitive transient receptor potential channels) belong to the TRP (transient receptor potential) channel superfamily. Emerging evidence implied that thermo-TRPs have been involved in regulation of cell fate in certain tumors. However, their distribution profiles and roles in melanoma remain incompletely understood. Methods . Western blot and digital PCR approaches were performed to identify the distribution profiles of six thermo-TRPs. MTT assessment was employed to detect cell viability. Flow cytometry was applied to test cell cycle and apoptosis. Calcium imaging was used to determine the function of channels. Five cell lines, including one normal human primary epidermal melanocytes and two human malignant melanoma (A375, G361) and two human metastatic melanoma (A2058, SK-MEL-3) cell lines, were chosen for this research. Results . In the present study, six thermo-TRPs including TRPV1/2/3/4, TRPA1, and TRPM8 were examined in human primary melanocytes and melanoma cells. We found that TRPV2/4, TRPA1, and TRPM8 exhibited ectopic distribution both in melanocytes and melanoma cells. Moreover, activation of TRPV2 and TRPV4 could lead to the decline of cell viability for melanoma A2058 and A375 cells. Subsequently, activation of TRPV2 by 2-APB (IC 50 = 150 μ M) induced cell necrosis in A2058 cells, while activation of TRPV4 by GSK1016790A (IC 50 = 10 nM) enhanced apoptosis of A375 cells. Furthermore, TRPV4 mediated cell apoptosis of melanoma via phosphorylation of AKT and was involved in calcium regulation. Conclusion . Overall, our studies revealed that TRPV4 and TRPV2 mediated melanoma cell death via channel activation and characterized the mechanism of functional TRPV4 ion channel in regulating AKT pathway driven antitumor process. Thus, they may serve as potential biomarkers for the prognosis and are targeted for the therapeutic use in human melanoma. ","author":[{"dropping-particle":"","family":"Zheng","given":"Jiaojiao","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Liu","given":"Fangyuan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Du","given":"Sha","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Li","given":"Mei","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wu","given":"Tian","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tan","given":"Xuejing","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cheng","given":"Wei","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of Oncology","id":"ITEM-1","issued":{"date-parts":[["2019"]]},"title":"Mechanism for Regulation of Melanoma Cell Death via Activation of Thermo-TRPV4 and TRPV2","type":"article-journal","volume":"2019"},"uris":["http://www.mendeley.com/documents/?uuid=19136f11-f311-4035-87ef-2e46eb372fd0"]}],"mendeley":{"formattedCitation":"(Zheng et al., 2019)","plainTextFormattedCitation":"(Zheng et al., 2019)","previouslyFormattedCitation":"(Zheng et al., 2019)"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(Zheng et al., 2019). La expresión de los canales de potasio cardiacos KCNE1, KCNE2, KCNA5, KCND3 y KCNJ11 ha sido relacionada con apnea del sueño y riesgo cardiovascular. ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1161/JAHA.116.003666","ISSN":"20479980","abstract":"© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell. Background: Cardiac arrhythmias and sudden cardiac death are more frequent in patients with obstructive sleep apnea (OSA). OSA is associated with QT prolongation, and QT prolongation is an independent risk factor for sudden cardiac death. Because QT prolongation can be mediated by potassium channel loss of function, we tested whether OSA or continuous positive airway pressure therapy altered mRNA expression of circulating white blood cell potassium channels. Methods and Results: In total, 28 patients with OSA newly diagnosed by polysomnogram and 6 participants without OSA were enrolled. Potassium channel levels in white blood cells at baseline and at a 4-week follow-up visit were compared. There was a significant inverse correlation between the severity of the OSA stratified by apnea-hypopnea index and mRNA expression of the main potassium channels assessed: KCNQ1 (r=-0.486, P=0.007), KCNH2 (r=-0.437, P=0.016), KCNE1 (r=-0.567, P=0.001), KCNJ2 (r=-0.442, P=0.015), and KCNA5 (r=-0.468, P=0.009). In addition, KCNQ1, KCNH2, and KCNE1 inversely correlated with the oxygen desaturation index 4. After 4 weeks of continuous positive airway pressure therapy, circulating KCNQ1 and KCNJ2 were increased 1.4±0.4-fold (P=0.040) and 2.1±1.4-fold (P=0.046) in the moderate OSA group. Compared with patients with mild or moderate OSA, patients with severe OSA had a persistently higher apnea-hypopnea index (mild 2.0±1.8, moderate 1.0±0.9, severe 5.8±5.6; P=0.015), perhaps explaining why the potassium channel changes were not seen in the severe OSA group. Conclusions: The mRNA expression of most potassium channels inversely correlates with the severity of OSA and hypoxemia. Continuous positive airway pressure therapy improves circulating KCNQ1 and KCNJ2 in patients with moderate OSA.","author":[{"dropping-particle":"","family":"Jiang","given":"Ning","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zhou","given":"Anyu","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Prasad","given":"Bharati","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zhou","given":"Li","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Doumit","given":"Jimmy","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shi","given":"Guangbin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Imran","given":"Hafiz","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kaseer","given":"Bahaa","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Millman","given":"Richard","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Dudley","given":"Samuel C.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of the American Heart Association","id":"ITEM-1","issue":"8","issued":{"date-parts":[["2016"]]},"page":"1-7","title":"Obstructive Sleep Apnea and Circulating Potassium Channel Levels","type":"article-journal","volume":"5"},"uris":["http://www.mendeley.com/documents/?uuid=fb7ebbe7-dd01-4c9e-a5ab-9e0727c2bcf2"]}],"mendeley":{"formattedCitation":"(Jiang et al., 2016)","plainTextFormattedCitation":"(Jiang et al., 2016)","previouslyFormattedCitation":"(Jiang et al., 2016)"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(Jiang et al., 2016). Se ha reportado que en glóbulos blancos se correlaciona de forma inversa con la severidad de la apnea del sueño, y el tratamiento con el dispositivo de presión positiva continua (CPAP) mejora la expresión de KCNQ1 y KCNJ2. Esto llevó a proponer que el nivel de expresión de estos canales puede ser un marcador de riesgo de arritmia en pacientes con apnea del sueño. De igual forma, muchos estudios recientes han evidenciado el potencial de los miRNAs como biomarcadores de diferentes tipos de patologías metabólicas, degenerativas y cancerosas, desde su diagnóstico hasta el tratamiento (P. Gazerani, 2019, Y. He et al., 2019, H. Wu et al., 2019), ya que se encuentran involucrados en la aparición y la progresión de varias enfermedades, haciéndolos clave en la patogénesis, diagnóstico, y respuesta al tratamiento, entre otros aspectos. Teniendo en cuenta que una característica importante de los biomarcadores es que utilicen muestras de fácil obtención y análisis, en este trabajo se plantea que el uso de leucocitos obtenidos de sangre periférica puede ser una fuente para evaluar cambios en la expresión de canales de la familia TRP y sus moléculas reguladoras, después de haber estado expuestos a hipoxia. En reportes previos se ha demostrado que los niveles circulantes de mRNA de canales de sodio cardiaco en leucocitos son representativos de los niveles de mRNA encontrados en miocardio, por lo cual se sugiere que los glóbulos blancos pueden experimentar condiciones similares a las que experimentan otro tipo de células del tejido cardiovascular ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1161/JAHA.116.003666","ISSN":"20479980","abstract":"© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell. Background: Cardiac arrhythmias and sudden cardiac death are more frequent in patients with obstructive sleep apnea (OSA). OSA is associated with QT prolongation, and QT prolongation is an independent risk factor for sudden cardiac death. Because QT prolongation can be mediated by potassium channel loss of function, we tested whether OSA or continuous positive airway pressure therapy altered mRNA expression of circulating white blood cell potassium channels. Methods and Results: In total, 28 patients with OSA newly diagnosed by polysomnogram and 6 participants without OSA were enrolled. Potassium channel levels in white blood cells at baseline and at a 4-week follow-up visit were compared. There was a significant inverse correlation between the severity of the OSA stratified by apnea-hypopnea index and mRNA expression of the main potassium channels assessed: KCNQ1 (r=-0.486, P=0.007), KCNH2 (r=-0.437, P=0.016), KCNE1 (r=-0.567, P=0.001), KCNJ2 (r=-0.442, P=0.015), and KCNA5 (r=-0.468, P=0.009). In addition, KCNQ1, KCNH2, and KCNE1 inversely correlated with the oxygen desaturation index 4. After 4 weeks of continuous positive airway pressure therapy, circulating KCNQ1 and KCNJ2 were increased 1.4±0.4-fold (P=0.040) and 2.1±1.4-fold (P=0.046) in the moderate OSA group. Compared with patients with mild or moderate OSA, patients with severe OSA had a persistently higher apnea-hypopnea index (mild 2.0±1.8, moderate 1.0±0.9, severe 5.8±5.6; P=0.015), perhaps explaining why the potassium channel changes were not seen in the severe OSA group. Conclusions: The mRNA expression of most potassium channels inversely correlates with the severity of OSA and hypoxemia. Continuous positive airway pressure therapy improves circulating KCNQ1 and KCNJ2 in patients with moderate OSA.","author":[{"dropping-particle":"","family":"Jiang","given":"Ning","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zhou","given":"Anyu","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Prasad","given":"Bharati","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zhou","given":"Li","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Doumit","given":"Jimmy","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shi","given":"Guangbin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Imran","given":"Hafiz","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kaseer","given":"Bahaa","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Millman","given":"Richard","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Dudley","given":"Samuel C.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of the American Heart Association","id":"ITEM-1","issue":"8","issued":{"date-parts":[["2016"]]},"page":"1-7","title":"Obstructive Sleep Apnea and Circulating Potassium Channel Levels","type":"article-journal","volume":"5"},"uris":["http://www.mendeley.com/documents/?uuid=fb7ebbe7-dd01-4c9e-a5ab-9e0727c2bcf2"]}],"mendeley":{"formattedCitation":"(Jiang et al., 2016)","plainTextFormattedCitation":"(Jiang et al., 2016)","previouslyFormattedCitation":"(Jiang et al., 2016)"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(Jiang et al., 2016). Ese planteamiento sugiere que las alteraciones encontradas en la expresión de canales iónicos en células sanguíneas pueden ser representativas de alteraciones encontradas en otro tipo de tejidos. Teniendo en cuenta esto, en este trabajo se propone el uso de leucocitos obtenidos de sangre periférica, para analizar la expresión de canales TRP que han sido asociados con enfermedades cardiovasculares. Como una etapa preliminar, en este trabajo se plantea analizar el efecto de la hipoxia sobre la expresión en leucocitos de los canales TRPC1, TRPC6 y TRPV4, así como los miRNAs que los regulan, los cuales tienen una relación directa con el desarrollo de alteraciones cardiovasculares. De acuerdo a eso, la pregunta de investigación que se quiere responder es cuál es el efecto de la hipoxia en la expresión de canales de la familia TRP y sus miRNAs reguladores en leucocitos obtenidos de sangre periférica. Esto permitirá establecer si los resultados son similares a los observados en células implicadas en la regulación de la actividad cardiovascular. Una de las alteraciones conocidas por su asociación con hipoxia es la apnea obstructiva del sueño, desorden reportado como factor de riesgo de enfermedades neurocognitivas y cardiovasculares. A pesar del rol que tienen diversos canales de la familia TRP en la homeostasis celular, no hay reportes que permitan relacionar su expresión con la apnea del sueño. Los resultados de este estudio permitirán evaluar la viabilidad del uso de leucocitos para analizar el efecto de patologías asociadas con la hipoxia, sobre la expresión y actividad de canales de la familia TRP. De acuerdo a los resultados que se obtengan en este proyecto, se espera proponer un estudio posterior en donde se analice si hay una relación directa entre la expresión y actividad de canales de la familia TRP y patologías como la apnea obstructiva del sueño, en la cual las células están sometidas a un estímulo de hipoxia.