{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T11:07:34Z","timestamp":1778843254556,"version":"3.51.4"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2016,11,24]],"date-time":"2016-11-24T00:00:00Z","timestamp":1479945600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2016,11,24]],"date-time":"2016-11-24T00:00:00Z","timestamp":1479945600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Hypertens Res"],"published-print":{"date-parts":[[2017,5]]},"DOI":"10.1038\/hr.2016.167","type":"journal-article","created":{"date-parts":[[2016,11,24]],"date-time":"2016-11-24T07:02:07Z","timestamp":1479970927000},"page":"441-449","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Epigenetic regulation of L-type voltage-gated Ca2+ channels in mesenteric arteries of aging hypertensive rats"],"prefix":"10.1038","volume":"40","author":[{"given":"Jingwen","family":"Liao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanyan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Ye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fanxing","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lijun","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,11,24]]},"reference":[{"key":"BFhr2016167_CR1","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1146\/annurev.med.46.1.27","volume":"46","author":"NM Kaplan","year":"1995","unstructured":"Kaplan NM . Hypertension in the elderly. Annu Rev Med 1995; 46: 27\u201335.","journal-title":"Annu Rev Med"},{"key":"BFhr2016167_CR2","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1097\/HCO.0b013e3280d357f9","volume":"22","author":"A Binder","year":"2007","unstructured":"Binder A . A review of the genetics of essential hypertension. Curr Opin Cardiol 2007; 22: 176\u2013184.","journal-title":"Curr Opin Cardiol"},{"key":"BFhr2016167_CR3","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1161\/HYPERTENSIONAHA.114.04456","volume":"65","author":"NL Sehgel","year":"2015","unstructured":"Sehgel NL, Sun Z, Hong Z, Hunter WC, Hill MA, Vatner DE, Vatner SF, Meininger GA . Augmented vascular smooth muscle cell stiffness and adhesion when hypertension is superimposed on aging. Hypertension 2015; 65: 370\u2013377.","journal-title":"Hypertension"},{"key":"BFhr2016167_CR4","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1161\/HYPERTENSIONAHA.114.03617","volume":"65","author":"Z Sun","year":"2015","unstructured":"Sun Z . Aging, arterial stiffness, and hypertension. Hypertension 2015; 65: 252\u2013256.","journal-title":"Hypertension"},{"key":"BFhr2016167_CR5","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1016\/j.tips.2009.04.008","volume":"30","author":"MA Hill","year":"2009","unstructured":"Hill MA, Meininger GA, Davis MJ, Laher I . Therapeutic potential of pharmacologically targeting arteriolar myogenic tone. Trends Pharmacol Sci 2009; 30: 363\u2013374.","journal-title":"Trends Pharmacol Sci"},{"key":"BFhr2016167_CR6","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1038\/hr.2015.56","volume":"38","author":"Y Chen","year":"2015","unstructured":"Chen Y, Zhang H, Zhang Y, Lu N, Zhang L, Shi L . Exercise intensity-dependent reverse and adverse remodeling of voltage-gated Ca2+ channels in mesenteric arteries from spontaneously hypertensive rats. Hypertens Res 2015; 38: 656\u2013665.","journal-title":"Hypertens Res"},{"key":"BFhr2016167_CR7","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1159\/000174250","volume":"20","author":"M Gollasch","year":"1997","unstructured":"Gollasch M, Nelson MT . Voltage-dependent Ca2+ channels in arterial smooth muscle cells. Kidney Blood Press Res 1997; 20: 355\u2013371.","journal-title":"Kidney Blood Press Res"},{"key":"BFhr2016167_CR8","doi-asserted-by":"publisher","first-page":"e97","DOI":"10.1161\/01.RES.0000131495.93500.3c","volume":"94","author":"A Pesic","year":"2004","unstructured":"Pesic A, Madden JA, Pesic M, Rusch NJ . High blood pressure upregulates arterial L-type Ca2+ channels: is membrane depolarization the signal? Circ Res 2004; 94: e97\u2013104.","journal-title":"Circ Res"},{"key":"BFhr2016167_CR9","doi-asserted-by":"publisher","first-page":"C1101","DOI":"10.1152\/ajpcell.00314.2013","volume":"306","author":"TV Saco","year":"2014","unstructured":"Saco TV, Parthasarathy PT, Cho Y, Lockey RF, Kolliputi N . Role of epigenetics in pulmonary hypertension. Am J Physiol Cell Physiol 2014; 306: C1101\u2013C1105.","journal-title":"Am J Physiol Cell Physiol"},{"key":"BFhr2016167_CR10","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1038\/ng1990","volume":"39","author":"M Weber","year":"2007","unstructured":"Weber M, Hellmann I, Stadler MB, Ramos L, Paabo S, Rebhan M, Schubeler D . Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome. Nat Genet 2007; 39: 457\u2013466.","journal-title":"Nat Genet"},{"key":"BFhr2016167_CR11","doi-asserted-by":"publisher","first-page":"17253","DOI":"10.1073\/pnas.1121249109","volume":"109","author":"LL Lam","year":"2012","unstructured":"Lam LL, Emberly E, Fraser HB, Neumann SM, Chen E, Miller GE, Kobor MS . Factors underlying variable DNA methylation in a human community cohort. Proc Natl Acad Sci USA 2012; 109: 17253\u201317260.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFhr2016167_CR12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s11010-014-2295-9","volume":"402","author":"F Pei","year":"2015","unstructured":"Pei F, Wang X, Yue R, Chen C, Huang J, Li X, Zeng C . Differential expression and DNA methylation of angiotensin type 1A receptors in vascular tissues during genetic hypertension development. Mol Cell Biochem 2015; 402: 1\u20138.","journal-title":"Mol Cell Biochem"},{"key":"BFhr2016167_CR13","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1002\/mnfr.201200636","volume":"58","author":"MB Glier","year":"2014","unstructured":"Glier MB, Green TJ, Devlin AM . Methyl nutrients, DNA methylation, and cardiovascular disease. Mol Nutr Food Res 2014; 58: 172\u2013182.","journal-title":"Mol Nutr Food Res"},{"key":"BFhr2016167_CR14","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1111\/acel.12349","volume":"14","author":"MJ Jones","year":"2015","unstructured":"Jones MJ, Goodman SJ, Kobor MS . DNA methylation and healthy human aging. Aging Cell 2015; 14: 924\u2013932.","journal-title":"Aging Cell"},{"key":"BFhr2016167_CR15","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s12915-015-0118-4","volume":"13","author":"M Jung","year":"2015","unstructured":"Jung M, Pfeifer GP . Aging and DNA methylation. BMC Biol 2015; 13: 7\u201315.","journal-title":"BMC Biol"},{"key":"BFhr2016167_CR16","doi-asserted-by":"publisher","first-page":"e9","DOI":"10.1111\/j.1755-5922.2010.00220.x","volume":"30","author":"J Fiedler","year":"2012","unstructured":"Fiedler J, Gupta SK, Thum T . MicroRNA-based therapeutic approaches in the cardiovascular system. Cardiovasc Ther 2012; 30: e9\u2013e15.","journal-title":"Cardiovasc Ther"},{"key":"BFhr2016167_CR17","doi-asserted-by":"publisher","first-page":"1188","DOI":"10.1016\/j.drudis.2015.05.007","volume":"20","author":"L Shi","year":"2015","unstructured":"Shi L, Liao J, Liu B, Zeng F, Zhang L . Mechanisms and therapeutic potential of microRNAs in hypertension. Drug Discov Today 2015; 20: 1188\u20131204.","journal-title":"Drug Discov Today"},{"key":"BFhr2016167_CR18","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1007\/s11906-011-0235-6","volume":"14","author":"S Batkai","year":"2012","unstructured":"Batkai S, Thum T . MicroRNAs in hypertension: mechanisms and therapeutic targets. Curr Hypertens Rep 2012; 14: 79\u201387.","journal-title":"Curr Hypertens Rep"},{"key":"BFhr2016167_CR19","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.phrs.2013.04.003","volume":"75","author":"S Albinsson","year":"2013","unstructured":"Albinsson S, Sward K . Targeting smooth muscle microRNAs for therapeutic benefit in vascular disease. Pharmacol Res 2013; 75: 28\u201336.","journal-title":"Pharmacol Res"},{"key":"BFhr2016167_CR20","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.arr.2014.03.005","volume":"17","author":"R Menghini","year":"2014","unstructured":"Menghini R, Stohr R, Federici M . MicroRNAs in vascular aging and atherosclerosis. Ageing Res Rev 2014; 17: 68\u201378.","journal-title":"Ageing Res Rev"},{"key":"BFhr2016167_CR21","doi-asserted-by":"publisher","first-page":"324","DOI":"10.2174\/15701611113119990129","volume":"13","author":"F Jansen","year":"2015","unstructured":"Jansen F, Yang X, Nickenig G, Werner N, Vasa-Nicotera M . Role, function and therapeutic potential of microRNAs in vascular aging. Curr Vasc Pharmacol 2015; 13: 324\u2013330.","journal-title":"Curr Vasc Pharmacol"},{"key":"BFhr2016167_CR22","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1161\/HYPERTENSIONAHA.111.185413","volume":"59","author":"L Guo","year":"2012","unstructured":"Guo L, Qiu Z, Wei L, Yu X, Gao X, Jiang S, Tian H, Jiang C, Zhu D . The microRNA-328 regulates hypoxic pulmonary hypertension by targeting at insulin growth factor 1 receptor and L-type calcium channel-alpha1C. Hypertension 2012; 59: 1006\u20131013.","journal-title":"Hypertension"},{"key":"BFhr2016167_CR23","doi-asserted-by":"publisher","first-page":"2378","DOI":"10.1161\/CIRCULATIONAHA.110.958967","volume":"122","author":"Y Lu","year":"2010","unstructured":"Lu Y, Zhang Y, Wang N, Pan Z, Gao X, Zhang F, Shan H, Luo X, Bai Y, Sun L, Song W, Xu C, Wang Z, Yang B . MicroRNA-328 contributes to adverse electrical remodeling in atrial fibrillation. Circulation 2010; 122: 2378\u20132387.","journal-title":"Circulation"},{"key":"BFhr2016167_CR24","doi-asserted-by":"publisher","first-page":"1846","DOI":"10.1111\/bph.13035","volume":"172","author":"L Shi","year":"2015","unstructured":"Shi L, Zhang H, Chen Y, Liu Y, Lu N, Zhao T, Zhang L . Chronic exercise normalizes changes in Cav 1.2 and KCa 1.1 channels in mesenteric arteries from spontaneously hypertensive rats. Br J Pharmacol 2015; 172: 1846\u20131858.","journal-title":"Br J Pharmacol"},{"key":"BFhr2016167_CR25","doi-asserted-by":"publisher","first-page":"2681","DOI":"10.1038\/nprot.2006.425","volume":"1","author":"VA Golovina","year":"2006","unstructured":"Golovina VA, Blaustein MP . Preparation of primary cultured mesenteric artery smooth muscle cells for fluorescent imaging and physiological studies. Nat Protoc 2006; 1: 2681\u20132687.","journal-title":"Nat Protoc"},{"key":"BFhr2016167_CR26","first-page":"217","volume":"14","author":"M Garcia-Palmieri","year":"1995","unstructured":"Garcia-Palmieri M . Hypertension in old age. P R Health Sci J 1995; 14: 217\u2013221.","journal-title":"P R Health Sci J"},{"key":"BFhr2016167_CR27","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1161\/01.HYP.0000025877.23309.36","volume":"40","author":"PF Pratt","year":"2002","unstructured":"Pratt PF, Bonnet S, Ludwig LM, Bonnet P, Rusch NJ . Upregulation of L-type Ca2+ channels in mesenteric and skeletal arteries of SHR. Hypertension 2002; 40: 214\u2013219.","journal-title":"Hypertension"},{"key":"BFhr2016167_CR28","doi-asserted-by":"publisher","first-page":"1090","DOI":"10.1161\/01.RES.73.6.1090","volume":"73","author":"Y Ohya","year":"1993","unstructured":"Ohya Y, Abe I, Fujii K, Takata Y, Fujishima M . Voltage-dependent Ca2+ channels in resistance arteries from spontaneously hypertensive rats. Circ Res 1993; 73: 1090\u20131099.","journal-title":"Circ Res"},{"key":"BFhr2016167_CR29","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1124\/mi.6.6.3","volume":"6","author":"S Sonkusare","year":"2006","unstructured":"Sonkusare S, Fraer M, Marsh JD, Rusch NJ . Disrupting calcium channel expression to lower blood pressure: new targeting of a well-known channel. Mol Interv 2006; 6: 304\u2013310.","journal-title":"Mol Interv"},{"key":"BFhr2016167_CR30","doi-asserted-by":"publisher","first-page":"e88975","DOI":"10.1371\/journal.pone.0088975","volume":"9","author":"T Fukuda","year":"2014","unstructured":"Fukuda T, Kuroda T, Kono M, Miyamoto T, Tanaka M, Matsui T . Attenuation of L-type Ca2+ channel expression and vasomotor response in the aorta with age in both Wistar-Kyoto and spontaneously hypertensive rats. PLoS ONE 2014; 9: e88975.","journal-title":"PLoS ONE"},{"key":"BFhr2016167_CR31","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/j.mad.2005.12.001","volume":"127","author":"C del Corsso","year":"2006","unstructured":"del Corsso C, Ostrovskaya O, McAllister CE, Murray K, Hatton WJ, Gurney AM, Spencer NJ, Wilson SM . Effects of aging on Ca2+ signaling in murine mesenteric arterial smooth muscle cells. Mech Ageing Dev 2006; 127: 315\u2013323.","journal-title":"Mech Ageing Dev"},{"key":"BFhr2016167_CR32","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1093\/gerona\/glu145","volume":"70","author":"H Zhang","year":"2015","unstructured":"Zhang H, Yang H, Zhang C, Jing Y, Wang C, Liu C, Zhang R, Wang J, Zhang J, Zen K, Li D . Investigation of microRNA expression in human serum during the aging process. J Gerontol A Biol Sci Med Sci 2015; 70: 102\u2013109.","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"BFhr2016167_CR33","doi-asserted-by":"publisher","first-page":"944","DOI":"10.1016\/j.neurobiolaging.2009.04.020","volume":"32","author":"N Li","year":"2011","unstructured":"Li N, Bates DJ, An J, Terry DA, Wang E . Up-regulation of key microRNAs, and inverse down-regulation of their predicted oxidative phosphorylation target genes, during aging in mouse brain. Neurobiol Aging 2011; 32: 944\u2013955.","journal-title":"Neurobiol Aging"},{"key":"BFhr2016167_CR34","doi-asserted-by":"publisher","first-page":"5797521","DOI":"10.1155\/2016\/5797521","volume":"2016","author":"FA Choudry","year":"2016","unstructured":"Choudry FA, Frontini M . Epigenetic control of haematopoietic stem cell aging and its clinical implications. Stem Cells Int 2016; 2016: 5797521.","journal-title":"Stem Cells Int"},{"key":"BFhr2016167_CR35","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1161\/CIRCEP.114.001709","volume":"7","author":"A Barana","year":"2014","unstructured":"Barana A, Matamoros M, Dolz-Gaiton P, Perez-Hernandez M, Amoros I, Nunez M, Sacristan S, Pedraz A, Pinto A, Fernandez-Aviles F, Tamargo J, Delpon E, Caballero R . Chronic atrial fibrillation increases microRNA-21 in human atrial myocytes decreasing L-type calcium current. Circ Arrhythm Electrophysiol 2014; 7: 861\u2013868.","journal-title":"Circ Arrhythm Electrophysiol"},{"key":"BFhr2016167_CR36","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1038\/nsmb.2067","volume":"18","author":"F Rau","year":"2011","unstructured":"Rau F, Freyermuth F, Fugier C, Villemin JP, Fischer MC, Jost B, Dembele D, Gourdon G, Nicole A, Duboc D, Wahbi K, Day JW, Fujimura H, Takahashi MP, Auboeuf D, Dreumont N, Furling D, Charlet-Berguerand N . Misregulation of miR-1 processing is associated with heart defects in myotonic dystrophy. Nat Struct Mol Biol 2011; 18: 840\u2013845.","journal-title":"Nat Struct Mol Biol"},{"key":"BFhr2016167_CR37","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.pcad.2004.04.006","volume":"47","author":"E Grossman","year":"2004","unstructured":"Grossman E, Messerli FH . Calcium antagonists. Prog Cardiovasc Dis 2004; 47: 34\u201357.","journal-title":"Prog Cardiovasc Dis"},{"key":"BFhr2016167_CR38","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1097\/MJT.0b013e31815db6c0","volume":"17","author":"N Meka","year":"2010","unstructured":"Meka N, Katragadda S, Cherian B, Arora RR . Combination therapy in hypertension: a focus on angiotensin receptor blockers and calcium channel blockers. Am J Ther 2010; 17: 61\u201367.","journal-title":"Am J Ther"}],"container-title":["Hypertension Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/hr2016167","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/hr2016167.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/doifinder\/10.1038\/hr.2016.167","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/www.nature.com\/articles\/hr2016167.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T02:19:04Z","timestamp":1641003544000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/hr2016167"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,11,24]]},"references-count":38,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2017,5]]}},"alternative-id":["BFhr2016167"],"URL":"https:\/\/doi.org\/10.1038\/hr.2016.167","relation":{},"ISSN":["0916-9636","1348-4214"],"issn-type":[{"value":"0916-9636","type":"print"},{"value":"1348-4214","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,11,24]]},"assertion":[{"value":"6 May 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 September 2016","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 October 2016","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 November 2016","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"This content has been made available to all.","name":"free","label":"Free to read"}]}}