{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T11:24:32Z","timestamp":1774265072269,"version":"3.50.1"},"reference-count":25,"publisher":"Portland Press Ltd.","issue":"20","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,10,1]]},"abstract":"<jats:p>Endothelial dysfunction and impaired vascular relaxation represent a common cause of microvascular disease in patients with diabetes. Although multiple mechanisms underlying altered endothelial cell function in diabetes have been described, there is currently no specific and approved pharmacological treatment. In this edition of Clinical Science, Morales-Cano et al. characterize voltage-dependent K+ (Kv) channels as genes regulated by pharmacological activation of peroxisome proliferator-activated receptor-b\/d (PPARb\/d). Diabetes altered Kv channel function leading to impaired coronary artery relaxation, which was prevented by pharmacological activation of PPARb\/d. These studies highlight an important mechanism of vascular dysfunction in diabetes and point to a potential approach for therapy, particularly considering that PPARb\/d ligands have been developed and tested in small clinical trials.<\/jats:p>","DOI":"10.1042\/cs20160518","type":"journal-article","created":{"date-parts":[[2016,9,16]],"date-time":"2016-09-16T01:48:59Z","timestamp":1473990539000},"page":"1837-1839","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Vascular smooth muscle cell dysfunction in diabetes: nuclear receptors channel to relaxation"],"prefix":"10.1042","volume":"130","author":[{"given":"Genevi\u00e8ve","family":"Doyon","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, UPMC and University of Pittsburgh School of Medicine Pittsburgh, PA 15261, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dennis","family":"Bruemmer","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, UPMC and University of Pittsburgh School of Medicine Pittsburgh, PA 15261, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2016,9,15]]},"reference":[{"key":"2021113010430223200_B1","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1056\/NEJM199807233390404","article-title":"Mortality from coronary heart disease in subjects with type\u00a02 diabetes and in nondiabetic subjects with and without prior myocardial infarction","volume":"339","author":"Haffner","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"2021113010430223200_B2","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.2337\/diab.42.7.1017","article-title":"Impairment of coronary vascular reserve and ACh-induced coronary vasodilation in diabetic patients with angiographically normal coronary arteries and normal left ventricular systolic function","volume":"42","author":"Nitenberg","year":"1993","journal-title":"Diabetes"},{"key":"2021113010430223200_B3","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1007\/s11892-004-0075-8","article-title":"Oxidative stress and diabetic vascular complications","volume":"4","author":"Son","year":"2004","journal-title":"Curr. Diab. Rep."},{"key":"2021113010430223200_B4","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1111\/j.1540-8167.1994.tb01156.x","article-title":"The role of the membrane potential of endothelial and smooth muscle cells in the regulation of coronary blood flow","volume":"2","author":"Daut","year":"1994","journal-title":"J. Cardiovasc. Electrophysiol."},{"key":"2021113010430223200_B5","doi-asserted-by":"publisher","first-page":"H2371","DOI":"10.1152\/ajpheart.01279.2007","article-title":"Voltage-dependent K+ channels regulate the duration of reactive hyperemia in the canine coronary circulation","volume":"294","author":"Dick","year":"2008","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"2021113010430223200_B6","first-page":"H348","article-title":"Regulation of membrane potential and diameter by voltage-dependent K+ channels in rabbit myogenic cerebral arteries","volume":"269","author":"Knot","year":"1995","journal-title":"Am. J. Physiol."},{"key":"2021113010430223200_B7","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1093\/cvr\/cvv020","article-title":"Kv7 channels critically determine coronary artery reactivity: left-right differences and down-regulation by hyperglycaemia","volume":"106","author":"Morales-Cano","year":"2015","journal-title":"Cardiovasc. Res."},{"key":"2021113010430223200_B8","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1161\/CIRCULATIONAHA.111.032136","article-title":"Downregulation of Kv7.4 channel activity in primary and secondary hypertension","volume":"124","author":"Jepps","year":"2011","journal-title":"Circulation"},{"key":"2021113010430223200_B9","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1161\/HYPERTENSIONAHA.111.187427","article-title":"Reduced KCNQ4-encoded voltage-dependent potassium channel activity underlies impaired beta-adrenoceptor-mediated relaxation of renal arteries in hypertension","volume":"59","author":"Chadha","year":"2012","journal-title":"Hypertension"},{"key":"2021113010430223200_B10","doi-asserted-by":"publisher","first-page":"1090","DOI":"10.1161\/HYPERTENSIONAHA.113.01244","article-title":"Contribution of Kv7 channels to basal coronary flow and active response to ischemia","volume":"62","author":"Khanamiri","year":"2013","journal-title":"Hypertension"},{"key":"2021113010430223200_B11","doi-asserted-by":"crossref","DOI":"10.1042\/CS20160141","article-title":"Activation of PPARbeta\/delta prevents hyperglycemia-induced impairment of Kv7 channels and cAMP-mediated relaxation in rat coronary arteries","author":"Morales-Cano","year":"2016","journal-title":"Clin. Sci. (Lond)."},{"key":"2021113010430223200_B12","doi-asserted-by":"publisher","first-page":"11505","DOI":"10.1074\/jbc.M110580200","article-title":"Peroxisome proliferator-activated receptor delta is up-regulated during vascular lesion formation and promotes post-confluent cell proliferation in vascular smooth muscle cells","volume":"277","author":"Zhang","year":"2002","journal-title":"J. Biol. Chem."},{"key":"2021113010430223200_B13","doi-asserted-by":"publisher","first-page":"5306","DOI":"10.1073\/pnas.091021198","article-title":"A selective peroxisome proliferator-activated receptor delta agonist promotes reverse cholesterol transport","volume":"98","author":"Oliver","year":"2001","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021113010430223200_B14","doi-asserted-by":"publisher","first-page":"15924","DOI":"10.1073\/pnas.0306981100","article-title":"Activation of peroxisome proliferator-activated receptor delta induces fatty acid beta-oxidation in skeletal muscle and attenuates metabolic syndrome","volume":"100","author":"Tanaka","year":"2003","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021113010430223200_B15","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/S0092-8674(03)00269-1","article-title":"Peroxisome-proliferator-activated receptor delta activates fat metabolism to prevent obesity","volume":"113","author":"Wang","year":"2003","journal-title":"Cell"},{"key":"2021113010430223200_B16","doi-asserted-by":"publisher","first-page":"4277","DOI":"10.1073\/pnas.0708647105","article-title":"PPARdelta-mediated antiinflammatory mechanisms inhibit angiotensin II-accelerated atherosclerosis","volume":"105","author":"Takata","year":"2008","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021113010430223200_B17","doi-asserted-by":"publisher","first-page":"4271","DOI":"10.1073\/pnas.0711875105","article-title":"PPARdelta regulates multiple proinflammatory pathways to suppress atherosclerosis","volume":"105","author":"Barish","year":"2008","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021113010430223200_B18","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1126\/science.1087344","article-title":"Transcriptional repression of atherogenic inflammation: modulation by PPARdelta","volume":"302","author":"Lee","year":"2003","journal-title":"Science"},{"key":"2021113010430223200_B19","doi-asserted-by":"publisher","first-page":"332","DOI":"10.2337\/db07-1318","article-title":"Activation of peroxisome proliferator-activated receptor (PPAR)delta promotes reversal of multiple metabolic abnormalities, reduces oxidative stress, and increases fatty acid oxidation in moderately obese men","volume":"57","author":"Riserus","year":"2008","journal-title":"Diabetes"},{"key":"2021113010430223200_B20","doi-asserted-by":"publisher","first-page":"2289","DOI":"10.1161\/ATVBAHA.112.247890","article-title":"Lipid effects of peroxisome proliferator-activated receptor-delta agonist GW501516\u00a0in subjects with low high-density lipoprotein cholesterol: characteristics of metabolic syndrome","volume":"32","author":"Olson","year":"2012","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"2021113010430223200_B21","doi-asserted-by":"publisher","first-page":"2889","DOI":"10.1210\/jc.2011-1061","article-title":"MBX-8025, a novel peroxisome proliferator receptor-delta agonist: lipid and other metabolic effects in dyslipidemic overweight patients treated with and without atorvastatin","volume":"96","author":"Bays","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"2021113010430223200_B22","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1161\/HYPERTENSIONAHA.111.174490","article-title":"Antihypertensive effects of peroxisome proliferator-activated receptor-beta activation in spontaneously hypertensive rats","volume":"58","author":"Zarzuelo","year":"2011","journal-title":"Hypertension"},{"key":"2021113010430223200_B23","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1016\/j.freeradbiomed.2012.05.045","article-title":"Activation of peroxisome proliferator-activated receptor-beta\/-delta (PPARbeta\/delta) prevents endothelial dysfunction in type\u00a01 diabetic rats","volume":"53","author":"Quintela","year":"2012","journal-title":"Free Radic. Biol. Med."},{"key":"2021113010430223200_B24","doi-asserted-by":"publisher","first-page":"3089","DOI":"10.1111\/bph.12646","article-title":"PPARbeta activation restores the high glucose-induced impairment of insulin signalling in endothelial cells","volume":"171","author":"Quintela","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"2021113010430223200_B25","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1016\/j.jmb.2007.06.091","article-title":"Three members of the human pyruvate dehydrogenase kinase gene family are direct targets of the peroxisome proliferator-activated receptor beta\/delta","volume":"372","author":"Degenhardt","year":"2007","journal-title":"J. Mol. Biol."}],"container-title":["Clinical Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/130\/20\/1837\/447957\/cs1301837.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/130\/20\/1837\/447957\/cs1301837.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T11:32:15Z","timestamp":1638271935000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/clinsci\/article\/130\/20\/1837\/71423\/Vascular-smooth-muscle-cell-dysfunction-in"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,9,15]]},"references-count":25,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2016,10,1]]}},"URL":"https:\/\/doi.org\/10.1042\/cs20160518","relation":{},"ISSN":["0143-5221","1470-8736"],"issn-type":[{"value":"0143-5221","type":"print"},{"value":"1470-8736","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,9,15]]}}}