{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:07:11Z","timestamp":1787242031042,"version":"build-2736575974"},"reference-count":126,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2018,3,10]],"date-time":"2018-03-10T00:00:00Z","timestamp":1520640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Diabetes mellitus is one the strongest risk factors for cardiovascular disease and, in particular, for ischemic heart disease (IHD). The pathophysiology of myocardial ischemia in diabetic patients is complex and not fully understood: some diabetic patients have mainly coronary stenosis obstructing blood flow to the myocardium; others present with coronary microvascular disease with an absence of plaques in the epicardial vessels. Ion channels acting in the cross-talk between the myocardial energy state and coronary blood flow may play a role in the pathophysiology of IHD in diabetic patients. In particular, some genetic variants for ATP-dependent potassium channels seem to be involved in the determinism of IHD.<\/jats:p>","DOI":"10.3390\/ijms19030802","type":"journal-article","created":{"date-parts":[[2018,3,12]],"date-time":"2018-03-12T13:13:48Z","timestamp":1520860428000},"page":"802","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["Diabetes Mellitus and Ischemic Heart Disease: The Role of Ion Channels"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6211-4482","authenticated-orcid":false,"given":"Paolo","family":"Severino","sequence":"first","affiliation":[{"name":"Department of Cardiovascular, Respiratory, Nephrology, Anesthesiology and Geriatric Sciences, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"D\u2019Amato","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular, Respiratory, Nephrology, Anesthesiology and Geriatric Sciences, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucrezia","family":"Netti","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular, Respiratory, Nephrology, Anesthesiology and Geriatric Sciences, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariateresa","family":"Pucci","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular, Respiratory, Nephrology, Anesthesiology and Geriatric Sciences, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marialaura","family":"De Marchis","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular, Respiratory, Nephrology, Anesthesiology and Geriatric Sciences, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9401-7377","authenticated-orcid":false,"given":"Raffaele","family":"Palmirotta","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Clinical Oncology Oncogenomic Research Center, \u2018Aldo Moro\u2019 University of Bari, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Volterrani","sequence":"additional","affiliation":[{"name":"Department of Cardiac Rehabilitation, IRCCS San Raffaele, 00163 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Mancone","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular, Respiratory, Nephrology, Anesthesiology and Geriatric Sciences, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Fedele","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular, Respiratory, Nephrology, Anesthesiology and Geriatric Sciences, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,3,10]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2016). Global Report on Diabetes, World Health Organization."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"897","DOI":"10.2217\/fca.13.65","article-title":"Role of ion channels in coronary microcirculation: A review of the literature","volume":"9","author":"Fedele","year":"2013","journal-title":"Future Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1002\/cphy.c160016","article-title":"Regulation of Coronary Blood Flow","volume":"7","author":"Goodwill","year":"2017","journal-title":"Compr. Physiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/j.yjmcc.2011.08.028","article-title":"The coronary circulation and blood flow in left ventricular hypertrophy","volume":"52","author":"Camici","year":"2012","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1016\/0002-9149(72)90606-6","article-title":"Adolf Fick\u2013forgotten genius of cardiology","volume":"30","author":"Shapiro","year":"1972","journal-title":"Am. J. Cardiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1007\/s00395-012-0264-6","article-title":"Contribution of voltage-dependent K+ and Ca2+ channels to coronary pressure-flow autoregulation","volume":"107","author":"Berwick","year":"2012","journal-title":"Basic Res. Cardiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1159\/000067203","article-title":"Effects of insulin on coronary blood flow in anesthetized pigs","volume":"39","author":"Molinari","year":"2002","journal-title":"J. Vasc. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1161\/01.RES.65.2.343","article-title":"Nonuniform vasomotor responses of the coronary microcirculation to serotonin and vasopressin","volume":"65","author":"Lamping","year":"1989","journal-title":"Circ. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/S0735-1097(10)80097-X","article-title":"Histaminergic modulation of coronary vascular resistance: Are we missing a therapeutic adjunct for the treatment of myocardial ischemia?","volume":"17","author":"Kern","year":"1991","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"H2154","DOI":"10.1152\/ajpheart.00987.2004","article-title":"Coronary arteriolar vasoconstriction to angiotensin II is augmented in prediabetic metabolic syndrome via activation of AT1 receptors","volume":"288","author":"Zhang","year":"2005","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1007\/s00395-013-0387-4","article-title":"Role of genetic polymorphisms of ion channels in the pathophysiology of coronary microvascular dysfunction and ischemic heart disease","volume":"108","author":"Fedele","year":"2013","journal-title":"Basic Res. Cardiol."},{"key":"ref_12","doi-asserted-by":"crossref","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":"ref_13","doi-asserted-by":"crossref","first-page":"2614","DOI":"10.1161\/01.ATV.0000249408.55796.da","article-title":"Hydrogen peroxide: A feed-forward dilator that couples myocardial metabolism to coronary blood flow","volume":"26","author":"Saitoh","year":"2006","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"683","DOI":"10.3181\/0812-RM-350","article-title":"Altered mechanism of adenosine-induced coronary arteriolar dilation in early-stage metabolic syndrome","volume":"234","author":"Bender","year":"2009","journal-title":"Exp. Biol. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1111\/j.1549-8719.2010.00054.x","article-title":"Contribution of adenosine A2A and A2B receptors to ischemic coronary dilation: Role of KV and KATP channels","volume":"17","author":"Berwick","year":"2010","journal-title":"Microcirculation"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"H3720","DOI":"10.1152\/ajpheart.00436.2007","article-title":"Redox-dependent coronary metabolic dilation","volume":"293","author":"Saitoh","year":"2007","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1152\/physiol.00040.2005","article-title":"Calcium-activated potassium channels and the regulation of vascular tone","volume":"21","author":"Ledoux","year":"2006","journal-title":"Physiology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1111\/j.1476-5381.2009.00132.x","article-title":"Endothelial Ca2+-activated K+ channels in normal and impaired EDHF-dilator responses\u2014Relevance to cardiovascular pathologies and drug discovery","volume":"157","author":"Grgic","year":"2009","journal-title":"Br. J. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"S46","DOI":"10.1161\/CIRCULATIONAHA.107.755827","article-title":"Calcium-activated potassium channels contribute to human coronary microvascular dysfunction after cardioplegia arrest","volume":"118","author":"Feng","year":"2008","journal-title":"Circulation"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1258\/ebm.2009.009201","article-title":"Role of potassium channels in coronary vasodilation","volume":"235","author":"Dick","year":"2010","journal-title":"Exp. Biol. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1097\/00005344-199911000-00001","article-title":"A novel transduction mechanism mediating dopamine-induced vascular relaxation: Opening of BKCa channels by cyclic AMP-induced stimulation of the cyclic GMP-dependent protein kinase","volume":"34","author":"Han","year":"1999","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_22","first-page":"H1283","article-title":"Hydrogen peroxide relaxes porcine coronary arteries by stimulating BKCa channel activity","volume":"275","author":"Barlow","year":"1998","journal-title":"Am. J. Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"H475","DOI":"10.1152\/ajpheart.2000.279.2.H475","article-title":"H2O2 opens BKCa channels via the PLA2-arachidonic acid signaling cascade in coronary artery smooth muscle","volume":"279","author":"Barlow","year":"2000","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"H2255","DOI":"10.1152\/ajpheart.00487.2003","article-title":"Hydrogen peroxide induces endothelium-dependent and -independent coronary arteriolar dilation: Role of cyclooxygenase and potassium channels","volume":"285","author":"Thengchaisri","year":"2003","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1016\/0006-2952(95)98500-9","article-title":"Protein kinase c-independent inhibition of the Ca2+-activated K+ channel by angiotensin II and endothelin-1","volume":"49","author":"Minami","year":"1995","journal-title":"Biochem. Pharmacol."},{"key":"ref_26","first-page":"H912","article-title":"ANG II inhibits calcium-activated potassium channels from coronary smooth muscle in lipid bilayers","volume":"258","author":"Toro","year":"1990","journal-title":"Am. J. Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/0014-2999(91)90120-F","article-title":"Dual action of endothelin-1 on the Ca2+-activated K+ channel in smooth muscle cells of porcine coronary artery","volume":"194","author":"Hu","year":"1991","journal-title":"Eur. J. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"C708","DOI":"10.1152\/ajpcell.1992.262.3.C708","article-title":"U46619, a thromboxane A2 agonist, inhibits KCa channel activity from pig coronary artery","volume":"262","author":"Scornik","year":"1992","journal-title":"Am. J. Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1124\/jpet.104.074476","article-title":"Calcium-activated potassium channel triggers cardioprotection of ischemic preconditioning","volume":"312","author":"Cao","year":"2005","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1113\/jphysiol.1991.sp018725","article-title":"Sodium calcium exchange in cultured bovine pulmonary artery endothelial cells","volume":"440","author":"Sage","year":"1991","journal-title":"J. Physiol."},{"key":"ref_31","first-page":"103","article-title":"Cardiopatia ischemica","volume":"Volume 1","author":"Lanza","year":"2010","journal-title":"Medicina Interna Sistematica"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2459","DOI":"10.1161\/CIRCULATIONAHA.116.022194","article-title":"Clinical Update: Cardiovascular Disease in Diabetes Mellitus","volume":"133","author":"Wang","year":"2016","journal-title":"Circulation"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"413","DOI":"10.7326\/0003-4819-141-6-200409210-00006","article-title":"Association of hemoglobin A1c with cardiovascular disease and mortality in adults: The European prospective investigation into cancer in Norfolk","volume":"141","author":"Khaw","year":"2004","journal-title":"Ann. Intern. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1056\/NEJMoa0908359","article-title":"Glycated hemoglobin, diabetes and cardiovascular risk in nondiabetic adults","volume":"362","author":"Selvin","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1007\/s00125-011-2078-8","article-title":"Haemoglobin A1c levels and subsequent cardiovascular disease in persons without diabetes: A meta-analysis of prospective cohorts","volume":"54","author":"Purdy","year":"2011","journal-title":"Diabetologia"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Emerging Risk Factors Collaboration, Sarwar, N., and Gao, P. (2010). Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: A collaborative meta-analysis of 102 prospective studies. Lancet, 375, 2215\u20132222.","DOI":"10.1016\/S0140-6736(10)60484-9"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.2337\/diacare.21.7.1138","article-title":"Mortality in adults with and without diabetes in a national cohort of the U.S. population, 1971-1993","volume":"21","author":"Gu","year":"1998","journal-title":"Diabetes Care"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1056\/NEJM199807233390404","article-title":"Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction","volume":"339","author":"Haffner","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1136\/hrt.2006.097956","article-title":"Improved but still high short- and long-term mortality rates after myocardial infarction in patients with diabetes mellitus: A time-trend report from the Swedish Register of Information and Knowledge about Swedish Heart Intensive Care Admission","volume":"93","author":"Norhammar","year":"2007","journal-title":"Heart"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3863","DOI":"10.2337\/dc12-2455","article-title":"Long-term complications and mortality in youngonset diabetes: Type 2 diabetes is more hazardous and lethal than type 1 diabetes","volume":"36","author":"Constantino","year":"2013","journal-title":"Diabetes Care"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"798","DOI":"10.2337\/diacare.29.04.06.dc05-1433","article-title":"High risk of cardiovascular disease in patients with type 1 diabetes in the U.K.: A cohort study using the General Practice Research Database","volume":"29","author":"Fuller","year":"2006","journal-title":"Diabetes Care"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2239","DOI":"10.1016\/S0140-6736(17)30058-2","article-title":"Type 2 diabetes","volume":"389","author":"Chatterjee","year":"2017","journal-title":"Lancet"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1038\/nm.2538","article-title":"Atherosclerosis: Current pathogenesis and therapeutic options","volume":"17","author":"Weber","year":"2011","journal-title":"Nat. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1038\/nature10146","article-title":"Progress and challenges in translating the biology of atherosclerosis","volume":"473","author":"Libby","year":"2011","journal-title":"Nature"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/35008121","article-title":"Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage","volume":"404","author":"Nishikawa","year":"2000","journal-title":"Nature"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1161\/ATVBAHA.116.306256","article-title":"Pathology of Human Coronary and Carotid Artery Atherosclerosis and Vascular Calcification in Diabetes Mellitus Highlights","volume":"37","author":"Yahagi","year":"2017","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1148\/radiol.1090600","article-title":"Diabetes: Prognostic value of CT coronary angiography\u2014Comparison with a nondiabetic population","volume":"256","author":"Cademartiri","year":"2010","journal-title":"Radiology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1161\/01.ATV.0000131783.74034.97","article-title":"Morphologic findings of coronary atherosclerotic plaques in diabetics: A postmortem study","volume":"24","author":"Burke","year":"2004","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1161\/CIRCULATIONAHA.112.120402","article-title":"Association between coronary vascular dysfunction and cardiac mortality in patients with and without diabetes mellitus","volume":"126","author":"Murthy","year":"2012","journal-title":"Circulation"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"377","DOI":"10.4330\/wjc.v2.i11.377","article-title":"Coronary microvascular dysfunction in diabetes mellitus: A review","volume":"2","author":"Picchi","year":"2010","journal-title":"World J. Cardiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1007\/s11739-009-0234-7","article-title":"Molecular and clinical aspects of endothelial dysfunction in diabetes","volume":"4","author":"Nacci","year":"2009","journal-title":"Intern. Emerg. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"S145","DOI":"10.2337\/dc11-s209","article-title":"Heart in diabetes: A microvascular disease","volume":"34","author":"Laakso","year":"2011","journal-title":"Diabetes Care"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1016\/S0735-1097(03)00166-9","article-title":"Role of chronic hyperglycemia in the pathogenesis of coronary microvascular dysfunction in diabetes","volume":"41","author":"Janisse","year":"2003","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1016\/S0735-1097(97)00327-6","article-title":"Reduced myocardial flow reserve in non-insulin-dependent diabetes mellitus","volume":"30","author":"Yokoyama","year":"1997","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1161\/01.RES.87.12.1123","article-title":"Myocardial cell death in human diabetes","volume":"87","author":"Frustaci","year":"2000","journal-title":"Circ. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/s11010-013-1861-x","article-title":"Conundrum of pathogenesis of diabetic cardiomyopathy: Role of vascular endothelial dysfunction, reactive oxygen species, and mitochondria","volume":"386","author":"Joshi","year":"2014","journal-title":"Mol. Cell. Biochem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1161\/01.CIR.100.8.813","article-title":"Effects of autonomic neuropathy on coronary blood flow in patients with diabetes mellitus","volume":"100","author":"Landa","year":"1999","journal-title":"Circulation"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1161\/CIRCULATIONAHA.112.093245","article-title":"The assessment of endothelial function: From research into clinical practice","volume":"126","author":"Flammer","year":"2012","journal-title":"Circulation"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1097\/FJC.0000000000000362","article-title":"Endothelial dysfunction in resistance arteries of hypertensive humans: Old and new conspirators","volume":"67","author":"Virdis","year":"2016","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1161\/01.CIR.0000153339.27064.14","article-title":"Endothelial function: Cardiac events","volume":"111","author":"Lerman","year":"2005","journal-title":"Circulation"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1161\/CIRCRESAHA.111.261388","article-title":"Aging and Atherosclerosis: Mechanisms, Functional Consequences, and Potential Therapeutics for Cellular Senescence","volume":"111","author":"Wang","year":"2012","journal-title":"Circ. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1006\/bbrc.1993.2153","article-title":"Reduction of nitric oxide producing activity associated with in vitro aging in cultured human umbilical vein endothelial cell","volume":"195","author":"Sato","year":"1993","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"H425","DOI":"10.1152\/ajpheart.00689.2008","article-title":"Vascular endothelial dysfunction with aging: Endothelin-1 and endothelial nitric oxide synthase","volume":"297","author":"Donato","year":"2009","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Khaidakov, M., Wang, X., and Mehta, J.L. (2011). Potential involvement of LOX-1 in functional consequences of endothelial senescence. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0020964"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.cjca.2012.06.023","article-title":"The biological role of inflammation in atherosclerosis","volume":"28","author":"Wong","year":"2012","journal-title":"Can. J. Cardiol."},{"key":"ref_66","first-page":"292","article-title":"Systemic inflammation and early atheroma formation: Are they related?","volume":"5","author":"Balanescu","year":"2010","journal-title":"Maedica"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3918","DOI":"10.1002\/art.22265","article-title":"Relationship of antiphospholipid antibodies to cardiovascular manifestations of systemic lupus erythematosus","volume":"54","author":"Roman","year":"2006","journal-title":"Arthritis Rheumatol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1097\/00001573-200009000-00008","article-title":"Low density lipoprotein oxidation, antioxidants, and atherosclerosis","volume":"15","author":"Catapano","year":"2000","journal-title":"Curr. Opin. Cardiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1146\/annurev.iy.12.040194.005015","article-title":"Tolerance, danger, and the extended family","volume":"12","author":"Matzinger","year":"1994","journal-title":"Annu. Rev. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/S1097-2765(02)00599-3","article-title":"The inflammasome: A molecular plat-form triggering activation of inflammatory caspases and processing of proIL-\u03b2","volume":"10","author":"Martinon","year":"2002","journal-title":"Mol. Cell"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1182\/blood.V87.6.2095.bloodjournal8762095","article-title":"Biologic basis for interleukin-1 in disease","volume":"87","author":"Dinarello","year":"1996","journal-title":"Blood"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1161\/01.CIR.0000151875.21836.AE","article-title":"Depletion of endothelial progenitor cells in the peripheral blood of patients with rheumatoid arthritis","volume":"111","author":"Grisar","year":"2005","journal-title":"Circulation"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Su, W., Li, W., Chen, H., Liu, H., Huang, H., and Li, H. (2015). Advanced Glycation End Products Impair Voltage-Gated K+ Channels-Mediated Coronary Vasodilation in Diabetic Rats. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0142865"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s00232-014-9741-1","article-title":"SPAK and OSR1 Sensitivity of Voltage-Gated K+ Channel Kv1.5","volume":"248","author":"Elvira","year":"2015","journal-title":"J. Membr. Biol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.taap.2014.10.019","article-title":"High level of oxygen treatment causes cardiotoxicity with arrhythmias and redox modulation","volume":"282","author":"Chapalamadugu","year":"2015","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1950","DOI":"10.1253\/circj.CJ-13-1587","article-title":"Cardiomyocyte-derived mitochondrial superoxide causes myocardial electrical remodeling by downregulating potassium channels and related molecules","volume":"78","author":"Kurokawa","year":"2014","journal-title":"Circ. J."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"10853","DOI":"10.1074\/jbc.M113.520940","article-title":"Regulation of large conductance Ca2+-activated K+ (BK) channel \u03b21 subunit expression by muscle RING finger protein 1 in diabetic vessels","volume":"289","author":"Yi","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1177\/1479164117703903","article-title":"Regulation of vascular large-conductance calcium-activated potassium channels by Nrf2 signalling","volume":"14","author":"Li","year":"2017","journal-title":"Diabetes Vasc. Dis. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e002062","DOI":"10.1161\/JAHA.115.002062","article-title":"Inactivation of Endothelial Small\/Intermediate Conductance of Calcium-Activated Potassium Channels Contributes to Coronary Arteriolar Dysfunction in Diabetic Patients","volume":"4","author":"Liu","year":"2015","journal-title":"J. Am. Heart Assoc."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1139\/apnm-2016-0048","article-title":"Coronary arterial BK channel dysfunction exacerbates ischemia\/reperfusion-induced myocardial injury in diabetic mice","volume":"41","author":"Lu","year":"2016","journal-title":"Appl. Physiol. Nutr. Metab."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1126\/science.270.5239.1166","article-title":"Reconstitution of IKATP: An inward rectifier subunit plus the sulfonylurea receptor","volume":"270","author":"Inagaki","year":"1995","journal-title":"Science"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1038\/nrendo.2013.166","article-title":"KATP channels and islet hormone secretion: New insights and controversies","volume":"9","author":"Ashcroft","year":"2013","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1111\/1753-0407.12565","article-title":"Prediabetes is associated with genetic variations in the gene encoding the Kir6.2 subunit of the pancreatic ATP-sensitive potassium channel (KCNJ11): A case-control study in a Han Chinese youth population","volume":"10","author":"Xu","year":"2018","journal-title":"J. Diabetes"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1007\/BF02658512","article-title":"Sequence variations in the human Kir6.2 gene, a subunit of the \u03b2-cell ATP-sensitive K-channel: No association with NIDDM in while Caucasian subjects or evidence of abnormal function when expressed in vitro","volume":"39","author":"Sakura","year":"1996","journal-title":"Diabetologia"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"568","DOI":"10.2337\/diabetes.52.2.568","article-title":"Large-scale association studies of variants in genes encoding the pancreatic \u03b2-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) confirm that the KCNJ11 E23K variant is associated with type 2 diabetes","volume":"52","author":"Gloyn","year":"2003","journal-title":"Diabetes"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2854","DOI":"10.2337\/diabetes.51.9.2854","article-title":"The prevalent Glu23Lys polymorphism in the potassium inward rectifier 6.2 (KIR6.2) gene is associated with impaired glucagon suppression in response to hyperglycemia","volume":"51","author":"Tschritter","year":"2002","journal-title":"Diabetes"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/S0092-8674(00)80701-1","article-title":"Targeted overactivity of \u03b2 cell KATP channels induces profound neonatal diabetes","volume":"100","author":"Koster","year":"2000","journal-title":"Cell"},{"key":"ref_88","first-page":"80","article-title":"Expression of an activating mutation in the gene encoding the KATP channel subunit Kir6.2 in mouse pancreatic \u03b2 cells recapitulates neonatal diabetes","volume":"119","author":"Girard","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.cmet.2008.12.005","article-title":"Secondary consequences of \u03b2 cell inexcitability: Identification and prevention in a murine model of KATP-induced neonatal diabetes mellitus","volume":"9","author":"Remedi","year":"2009","journal-title":"Cell Metab."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"E671","DOI":"10.1152\/ajpendo.00492.2002","article-title":"Glucagon and regulation of glucose metabolism","volume":"284","author":"Jiang","year":"2003","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.diabres.2013.11.019","article-title":"Glucose regulation of glucagon secretion","volume":"103","author":"Gylfe","year":"2014","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4103\/2277-9175.148256","article-title":"Association of KCNJ11 (E23K) gene polymorphism with susceptibility to type 2 diabetes in Iranian patients","volume":"4","author":"Rastegari","year":"2015","journal-title":"Adv. Biomed. Res."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Qiu, L., Na, R., Xu, R., Wang, S., Sheng, H., Wu, W., and Qu, Y. (2014). Quantitative assessment of the effect of KCNJ11 gene polymorphism on the risk of type 2 diabetes. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0093961"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Souza, S.W., Alcazar, L.P., Arakaki, P.A., Santos-Weiss, I.C.R., Alberton, D., Picheth, G., and Rego, F.G.M. (2017). Polymorphism E23K (rs5219) in the KCNJ11 gene in Euro-Brazilian subjects with type 1 and 2 diabetes. Genet. Mol. Res., 16.","DOI":"10.4238\/gmr16029543"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2990","DOI":"10.4238\/2013.August.20.1","article-title":"Meta-analysis of association of common variants in the KCNJ11-ABCC8 region with type 2 diabetes","volume":"12","author":"Qin","year":"2013","journal-title":"Genet. Mol. Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2310","DOI":"10.2337\/db17-0149","article-title":"Genetic Variation at the Sulfonylurea Receptor, Type 2 Diabetes, and Coronary Heart Disease","volume":"66","author":"Emdin","year":"2017","journal-title":"Diabetes"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1001\/jama.281.21.2005","article-title":"UK Prospective Diabetes Study (UKPDS) Group. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: Progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group","volume":"281","author":"Turner","year":"1999","journal-title":"JAMA"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1002\/(SICI)1096-9896(200002)190:3<244::AID-PATH575>3.0.CO;2-8","article-title":"Nitric oxide in the pathogenesis of vascular disease","volume":"190","author":"Li","year":"2000","journal-title":"J. Pathol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1385\/CBB:38:3:323","article-title":"Differential responsiveness of vascular endothelial cells to different types of fluid mechanical shear stress","volume":"38","author":"Barakat","year":"2003","journal-title":"Cell Biochem. Biophys."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/labinvest.3700215","article-title":"The role of shear stress in the pathogenesis of atherosclerosis","volume":"85","author":"Cunningham","year":"2005","journal-title":"Lab. Investig."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"14871","DOI":"10.1073\/pnas.0406073101","article-title":"Distinct endothelial phenotypes evoked by arterial waveforms derived from atherosclerosis-susceptible and -resistant regions of human vasculature","volume":"101","author":"Dai","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2482","DOI":"10.1073\/pnas.0305938101","article-title":"Coexisting proinflammatory and antioxidative endothelial transcription profiles in a disturbed flow region of the adult porcine aorta","volume":"101","author":"Passerini","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1161\/hh0901.090440","article-title":"Anti-inflammatory mechanisms in the vascular wall","volume":"88","author":"Tedgui","year":"2001","journal-title":"Circ. Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1152\/physrev.1995.75.3.519","article-title":"Flow-mediated endothelial mechanotransduction","volume":"75","author":"Davies","year":"1995","journal-title":"Physiol. Rev."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1385\/CBB:46:3:277","article-title":"Flow-Activated Ion Channels in Vascular Endothelium","volume":"46","author":"Gautam","year":"2006","journal-title":"Cell Biochem. Biophys."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Jamwal, S., and Sharma, S. (2018). Vascular endothelium dysfunction: A conservative target in metabolic disorders. Inflamm. Res.","DOI":"10.1007\/s00011-018-1129-8"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1074\/jbc.275.1.585","article-title":"Kinase-dependent regulation of the intermediate conductance, calcium-dependent potassium channel, hIK1","volume":"275","author":"Gerlach","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/j.molcel.2006.11.012","article-title":"Histidine phosphorylation of the potassium channel KCa3.1 by nucleoside diphosphate kinase B is required for activation of KCa3.1 and CD4 T cells","volume":"24","author":"Srivastava","year":"2006","journal-title":"Mol. Cell."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"e3343","DOI":"10.1161\/01.RES.85.9.e33","article-title":"Molecular cloning, characterizationoftheintermediate-conductance Ca2+-activated K+ channel in vascular smooth muscle: Relationship between KCa channel diversity and smooth muscle cell function","volume":"85","author":"Neylon","year":"1999","journal-title":"Circ. Res."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/S0165-5728(01)00462-3","article-title":"Mononuclear phagocyte biophysiology influences brain transendothelial and tissue migration: Implication for HIV-1-associated dementia","volume":"122","author":"Chung","year":"2002","journal-title":"J. Neuroimmunol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"H2493","DOI":"10.1152\/ajpheart.01254.2005","article-title":"Upregulation of intermediate-conductance Ca2+-activated K+ channel (IKCa1) mediates phenotypic modulation of coronary smooth muscle","volume":"291","author":"Tharp","year":"2006","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.1182\/blood-2006-01-009613","article-title":"Reversible inhibition of the platelet procoagulant response through manipulation of the Gardos channel","volume":"108","author":"Wolfs","year":"2006","journal-title":"Blood"},{"key":"ref_113","first-page":"648","article-title":"Exenatide Inhibits the KCa3.1 Channels of Aortic Vascular Smooth Muscle in Diabetic Rats","volume":"33","author":"Dong","year":"2017","journal-title":"Acta Cardiol. Sin."},{"key":"ref_114","first-page":"A16586","article-title":"The intermediate conductance Ca2+-activated K+ channel KCa3.1 regulates proliferation of human coronary smooth muscle cells","volume":"126","author":"Bi","year":"2012","journal-title":"Circulation"},{"key":"ref_115","first-page":"155","article-title":"Role of KCa3.1 channels in proliferation and migration of vascular smooth muscle cells by diabetic rat serum","volume":"56","author":"Su","year":"2013","journal-title":"Chin. J. Physiol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.yjmcc.2011.03.014","article-title":"Insulin-mediated upregulation of K3.1 channels promotes cell migration and proliferation in rat vascular smooth muscle","volume":"51","author":"Su","year":"2011","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/labinvest.2012.163","article-title":"KCa3.1 channels mediate the increase of cell migration and proliferation by advanced glycation end products in cultured rat vascular smooth muscle cells","volume":"93","author":"Zhao","year":"2013","journal-title":"Lab. Investig."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1161\/ATVBAHA.116.308461","article-title":"Role of KCa3.1 Channels in Macrophage Polarization and Its Relevance in Atherosclerotic Plaque Instability","volume":"37","author":"Xu","year":"2017","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_119","first-page":"22","article-title":"Human myoblast differentiation: Ca2+ channels are activated by K+ channels","volume":"17","author":"Bernheim","year":"2002","journal-title":"News Physiol. Sci."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1111\/jcmm.12705","article-title":"Role of Kir2.1 in human monocyte-derived foam cell maturation","volume":"20","author":"Zhang","year":"2016","journal-title":"J. Cell. Mol. Med."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1093\/cvr\/cvq305","article-title":"Potent suppression of vascular smooth muscle cell migration and human neointimal hyperplasia by KV1.3 channel blockers","volume":"89","author":"Cheong","year":"2011","journal-title":"Cardiovasc. Res."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.abb.2015.12.013","article-title":"Kv1.3 potassium channel mediates macrophage migration in atherosclerosis by regulating ERK activity","volume":"591","author":"Kan","year":"2016","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1172\/JCI16921","article-title":"The voltage-gated Kv1.3 K+ channel in effector memory T cells as new target for MS","volume":"111","author":"Wulff","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1016\/j.bcp.2010.05.012","article-title":"Immunomodulatory effects of diclofenac in leukocytes through the targeting of Kv1.3 voltage-dependent potassium channels","volume":"80","author":"Villalonga","year":"2010","journal-title":"Biochem. Pharmacol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1007\/s00011-015-0855-4","article-title":"Usefulness of targeting lymphocyte Kv1.3-channels in the treatment of respiratory diseases","volume":"64","author":"Kazama","year":"2015","journal-title":"Inflamm. Res."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/j.atherosclerosis.2012.11.016","article-title":"Up-regulated ATP-sensitive potassium channels play a role in increased inflammation and plaque vulnerability in macrophages","volume":"226","author":"Ling","year":"2013","journal-title":"Atherosclerosis"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/3\/802\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T14:56:33Z","timestamp":1760194593000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/3\/802"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,10]]},"references-count":126,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2018,3]]}},"alternative-id":["ijms19030802"],"URL":"https:\/\/doi.org\/10.3390\/ijms19030802","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,10]]}}}