{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T03:51:34Z","timestamp":1773805894448,"version":"3.50.1"},"reference-count":84,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2021,9,9]],"date-time":"2021-09-09T00:00:00Z","timestamp":1631145600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006955","name":"Office of Extramural Research, National Institutes of Health","doi-asserted-by":"publisher","award":["R01EY018420"],"award-info":[{"award-number":["R01EY018420"]}],"id":[{"id":"10.13039\/100006955","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014109","name":"Baylor Scott and White Health","doi-asserted-by":"publisher","award":["Kruse Chair Fund"],"award-info":[{"award-number":["Kruse Chair Fund"]}],"id":[{"id":"10.13039\/100014109","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Protein kinase C (PKC) activation can evoke vasoconstriction and contribute to coronary disease. However, it is unclear whether PKC activation, without activating the contractile machinery, can lead to coronary arteriolar dysfunction. The vasoconstriction induced by the PKC activator phorbol 12,13-dibutyrate (PDBu) was examined in isolated porcine coronary arterioles. The PDBu-evoked vasoconstriction was sensitive to a broad-spectrum PKC inhibitor but not affected by inhibiting PKC\u03b22 or Rho kinase. After exposure of the vessels to a sub-vasomotor concentration of PDBu (1 nmol\/L, 60 min), the endothelium-dependent nitric oxide (NO)-mediated dilations in response to serotonin and adenosine were compromised but the dilation induced by the NO donor sodium nitroprusside was unaltered. PDBu elevated superoxide production, which was blocked by the superoxide scavenger Tempol. The impaired NO-mediated vasodilations were reversed by Tempol or inhibition of PKC\u03b22, xanthine oxidase, c-Jun N-terminal kinase (JNK) and Rho kinase but were not affected by a hydrogen peroxide scavenger or inhibitors of NAD(P)H oxidase and p38 kinase. The PKC\u03b22 protein was detected in the arteriolar wall and co-localized with endothelial NO synthase. In conclusion, activation of PKC\u03b22 appears to compromise NO-mediated vasodilation via Rho kinase-mediated JNK signaling and superoxide production from xanthine oxidase, independent of the activation of the smooth muscle contractile machinery.<\/jats:p>","DOI":"10.3390\/ijms22189763","type":"journal-article","created":{"date-parts":[[2021,9,9]],"date-time":"2021-09-09T12:20:37Z","timestamp":1631190037000},"page":"9763","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Activation of Coronary Arteriolar PKC\u03b22 Impairs Endothelial NO-Mediated Vasodilation: Role of JNK\/Rho Kinase Signaling and Xanthine Oxidase Activation"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0815-0743","authenticated-orcid":false,"given":"Naris","family":"Thengchaisri","sequence":"first","affiliation":[{"name":"Department of Medical Physiology, Cardiovascular Research Institute, College of Medicine, Texas A&M University Health Science Center, Bryan, TX 77807, USA"},{"name":"Department of Companion Animal Clinical Sciences, Faculty of Veterinary Medicine, Kasetsart University, Bangkok 10900, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Travis","family":"Hein","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology, Cardiovascular Research Institute, College of Medicine, Texas A&M University Health Science Center, Bryan, TX 77807, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology, Cardiovascular Research Institute, College of Medicine, Texas A&M University Health Science Center, Bryan, TX 77807, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4912-6910","authenticated-orcid":false,"given":"Lih","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology, Cardiovascular Research Institute, College of Medicine, Texas A&M University Health Science Center, Bryan, TX 77807, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1161\/01.ATV.0000155325.41507.e0","article-title":"Proatherosclerotic mechanisms involving protein kinase C in diabetes and insulin resistance","volume":"25","author":"King","year":"2005","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.biolcel.2004.04.012","article-title":"Possible involvement of protein kinase C activation in differentiation of human umbilical vein endothelium-derived cell into smooth muscle-like cell","volume":"96","author":"Ishisaki","year":"2004","journal-title":"Biol. Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"37919","DOI":"10.1074\/jbc.M111.251777","article-title":"Ca2+ influx through reverse mode Na+\/Ca2+ exchange is critical for vascular endothelial growth factor-mediated extracellular signal-regulated kinase (ERK) 1\/2 activation and angiogenic functions of human endothelial cells","volume":"286","author":"Andrikopoulos","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/S1537-1891(03)00007-7","article-title":"Role of Ca2+ signaling in the regulation of endothelial permeability","volume":"39","author":"Tiruppathi","year":"2002","journal-title":"Vasc. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"L809","DOI":"10.1152\/ajplung.00311.2005","article-title":"Control of intracellular trafficking of ICAM-1-targeted nanocarriers by endothelial Na+\/H+ exchanger proteins","volume":"290","author":"Muro","year":"2006","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5167","DOI":"10.1167\/iovs.18-25369","article-title":"Constriction of retinal venules to endothelin-1: Obligatory roles of ETA receptors, extracellular calcium entry, and rho kinase","volume":"59","author":"Chen","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"7587","DOI":"10.1167\/iovs.13-13178","article-title":"Role of endothelium in vasomotor responses to endothelin system and protein kinase C activation in porcine retinal arterioles","volume":"54","author":"Potts","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_8","first-page":"858","article-title":"Phorbol dibutyrate inhibits release and action of endothelium-derived relaxing factor(s) in canine blood vessels","volume":"249","author":"Rubanyi","year":"1989","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1007\/s00210-004-0975-9","article-title":"Inhibition of protein kinase C-mediated contraction by Rho kinase inhibitor fasudil in rabbit aorta","volume":"370","author":"Shimomura","year":"2004","journal-title":"Naunyn-Schmiedeberg Arch. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1111\/j.1440-1681.2008.05045.x","article-title":"A role for Rho-kinase in Ca2+-independent contractions induced by phorbol-12,13-dibutyrate","volume":"36","author":"Baek","year":"2009","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"H1048","DOI":"10.1152\/ajpheart.00491.2008","article-title":"Peroxide generation by p47phox-Src activation of Nox2 has a key role in protein kinase C-induced arterial smooth muscle contraction","volume":"296","author":"Gupte","year":"2009","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1291\/hypres.25.419","article-title":"Carvedilol inhibits pressure-induced increase in oxidative stress in coronary smooth muscle cells","volume":"25","author":"Yasunari","year":"2002","journal-title":"Hypertens. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1046\/j.1523-1755.1999.00725.x","article-title":"Differential expression of protein kinase C isoforms in streptozotocin-induced diabetic rats","volume":"56","author":"Kang","year":"1999","journal-title":"Kidney Int."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1161\/res.90.1.5","article-title":"Vascular dysfunction in hyperglycemia: Is protein kinase C the culprit?","volume":"90","author":"Gutterman","year":"2002","journal-title":"Circ. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1080\/10715760500073840","article-title":"Endothelial NO Synthase (eNOS) phosphorylation regulates coronary diameter during ischemia-reperfusion in association with oxidative stress","volume":"39","author":"Hoshino","year":"2005","journal-title":"Free Radic. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1249\/01.MSS.0000155698.76417.4C","article-title":"Exercise and hypercholesterolemia produce disparate shifts in coronary PKC expression","volume":"37","author":"Korzick","year":"2005","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1006\/jmcc.1999.1073","article-title":"The role of endothelin, protein kinase C and free radicals in the mechanism of the post-ischemic endothelial dysfunction in guinea-pig hearts","volume":"32","author":"Maczewski","year":"2000","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1161\/01.CIR.0000079165.84309.4D","article-title":"High pressure induces superoxide production in isolated arteries via protein kinase C-dependent activation of NAD(P)H oxidase","volume":"108","author":"Ungvari","year":"2003","journal-title":"Circulation"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1097\/00004872-200107000-00009","article-title":"Increased generation of superoxide by angiotensin II in smooth muscle cells from resistance arteries of hypertensive patients: Role of phospholipase D-dependent NAD(P)H oxidase-sensitive pathways","volume":"19","author":"Touyz","year":"2001","journal-title":"J. Hypertens."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.yjmcc.2015.07.014","article-title":"Endothelin-1 impairs coronary arteriolar dilation: Role of p38 kinase-mediated superoxide production from NADPH oxidase","volume":"86","author":"Thengchaisri","year":"2015","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.yjmcc.2005.11.010","article-title":"Activation of JNK and xanthine oxidase by TNF-\u03b1 impairs nitric oxide-mediated dilation of coronary arterioles","volume":"40","author":"Zhang","year":"2006","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1161\/01.ATV.0000159890.10526.1e","article-title":"C-reactive protein inhibits endothelium-dependent NO-mediated dilation in coronary arterioles by activating p38 kinase and NAD(P)H oxidase","volume":"25","author":"Qamirani","year":"2005","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.yjmcc.2019.04.015","article-title":"Requisite roles of LOX-1, JNK, and arginase in diabetes-induced endothelial vasodilator dysfunction of porcine coronary arterioles","volume":"131","author":"Hein","year":"2019","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1093\/cvr\/cvx103","article-title":"Enhanced endothelin-1\/Rho-kinase signalling and coronary microvascular dysfunction in hypertensive myocardial hypertrophy","volume":"113","author":"Tsai","year":"2017","journal-title":"Cardiovasc. Res."},{"key":"ref_25","unstructured":"Tuma, R.F., Duran, W.N., and Ley, K. (2008). Local Regulation of Microvascular Perfusion. Handbook of Physiology, Section 2: The Cardiovascular System. Microcirculation, American Physiological Society. [2nd ed.]. Pt. 2, Chpt. 6."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S0014-5793(98)01455-0","article-title":"The effects of the Rho-kinase inhibitor Y-27632 on arachidonic acid-, GTPgammaS-, and phorbol ester-induced Ca2+-sensitization of smooth muscle","volume":"440","author":"Fu","year":"1998","journal-title":"FEBS Lett."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1113\/jphysiol.2002.031823","article-title":"Smooth muscle membrane potential modulates endothelium-dependent relaxation of rat basilar artery via myo-endothelial gap junctions","volume":"545","author":"Allen","year":"2002","journal-title":"J. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1111\/j.1549-8719.2012.00187.x","article-title":"Endothelial feedback and the myoendothelial projection","volume":"19","author":"Kerr","year":"2012","journal-title":"Microcirculation"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1126\/scisignal.aal3806","article-title":"Voltage-dependent Ca2+ entry into smooth muscle during contraction promotes endothelium-mediated feedback vasodilation in arterioles","volume":"10","author":"Garland","year":"2017","journal-title":"Sci. Signal."},{"key":"ref_30","first-page":"55","article-title":"Endothelial regulation of coronary microvascular tone under physiological and pathophysiological conditions","volume":"14","author":"Chilian","year":"1993","journal-title":"Eur. Heart J."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Poznyak, A., Grechko, A.V., Poggio, P., Myasoedova, V.A., Alfieri, V., and Orekhov, A.N. (2020). The diabetes mellitus-atherosclerosis connection: The role of lipid and glucose metabolism and chronic inflammation. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21051835"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.jss.2008.02.022","article-title":"PKC and MLCK-dependent, cytokine-induced rat coronary endothelial dysfunction","volume":"152","author":"Tinsley","year":"2009","journal-title":"J. Surg. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1161\/01.HYP.37.2.561","article-title":"Oxidized-LDL enhances coronary vasoconstriction by increasing the activity of protein kinase C isoforms alpha and epsilon","volume":"37","author":"Giardina","year":"2001","journal-title":"Hypertension"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1161\/01.ATV.0000104010.87348.26","article-title":"Evidence for protein kinase C-mediated activation of Rho-kinase in a porcine model of coronary artery spasm","volume":"23","author":"Kandabashi","year":"2003","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"407","DOI":"10.3390\/ph6030407","article-title":"Protein kinase C inhibitors as modulators of vascular function and their application in vascular disease","volume":"6","author":"Khalil","year":"2013","journal-title":"Pharmaceuticals"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Velnati, S., Centonze, S., Girivetto, F., Capello, D., Biondi, R.M., Bertoni, A., Cantello, R., Ragnoli, B., Malerba, M., and Graziani, A. (2021). Identification of key phospholipids that bind and activate atypical PKCs. Biomedicines, 9.","DOI":"10.3390\/biomedicines9010045"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2425","DOI":"10.1161\/01.CIR.90.5.2425","article-title":"Role of protein kinase C-mediated pathway in the pathogenesis of coronary artery spasm in a swine model","volume":"90","author":"Ito","year":"1994","journal-title":"Circulation"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1016\/j.bcp.2005.07.017","article-title":"Protein kinase C isoforms as specific targets for modulation of vascular smooth muscle function in hypertension","volume":"70","author":"Salamanca","year":"2005","journal-title":"Biochem. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1124\/jpet.105.100040","article-title":"Segmental differences in the roles of rho-kinase and protein kinase C in mediating vasoconstriction","volume":"317","author":"Budzyn","year":"2006","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3691","DOI":"10.2337\/db16-0248","article-title":"Activation of the pro-oxidant PKC\u03b22-p66Shc signaling pathway contributes to pericyte dysfunction in skeletal muscles of patients with diabetes with critical limb ischemia","volume":"65","author":"Vono","year":"2016","journal-title":"Diabetes"},{"key":"ref_41","first-page":"1273","article-title":"A carboxy-terminal deletion mutant of protein kinase C\u03b2II inhibits insulin-stimulated 2-deoxyglucose uptake in L6 rat skeletal muscle cells","volume":"10","author":"Chalfant","year":"1996","journal-title":"Mol. Endocrinol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1161\/01.CIR.0000133384.38551.A8","article-title":"Selective inhibition of protein kinase C\u03b22 prevents acute effects of high glucose on vascular cell adhesion molecule-1 expression in human endothelial cells","volume":"110","author":"Kouroedov","year":"2004","journal-title":"Circulation"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1167\/iovs.07-1387","article-title":"C-reactive protein inhibits endothelium-dependent nitric oxide-mediated dilation of retinal arterioles via enhanced superoxide production","volume":"49","author":"Nagaoka","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"G723","DOI":"10.1152\/ajpgi.00473.2012","article-title":"Role of PKC and RhoA\/ROCK pathways in the spontaneous phasic activity in the rectal smooth muscle","volume":"304","author":"Singh","year":"2013","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1167\/iovs.06-0856","article-title":"Simvastatin elicits dilation of isolated porcine retinal arterioles: Role of nitric oxide and mevalonate-rho kinase pathways","volume":"48","author":"Nagaoka","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1165\/rcmb.2011-0449OC","article-title":"High glucose enhances responsiveness of human airways smooth muscle via the Rho\/ROCK pathway","volume":"47","author":"Cazzola","year":"2012","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1124\/jpet.106.110635","article-title":"Novel Rho kinase inhibitors with anti-inflammatory and vasodilatory activities","volume":"320","author":"Doe","year":"2007","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1161\/01.CIR.92.3.518","article-title":"Longitudinal gradients for endothelium-dependent and -independent vascular responses in the coronary microcirculation","volume":"92","author":"Kuo","year":"1995","journal-title":"Circulation"},{"key":"ref_49","first-page":"H1706","article-title":"Interaction of pressure- and flow-induced responses in porcine coronary resistance vessels","volume":"261","author":"Kuo","year":"1991","journal-title":"Am. J. Physiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1161\/01.RES.70.3.465","article-title":"Pathophysiological consequences of atherosclerosis extend into the coronary microcirculation. Restoration of endothelium-dependent responses by L-arginine","volume":"70","author":"Kuo","year":"1992","journal-title":"Circ. Res."},{"key":"ref_51","first-page":"655","article-title":"Adenosine A2A receptors mediate coronary microvascular dilation to adenosine: Role of nitric oxide and ATP-sensitive potassium channels","volume":"291","author":"Hein","year":"1999","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"H492","DOI":"10.1152\/ajpheart.00818.2003","article-title":"Protein kinase \u03b2II in Zucker obese rats compromises oxygen and flow-mediated regulation of nitric oxide formation","volume":"286","author":"Bohlen","year":"2004","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"301","DOI":"10.2174\/1568006033481375","article-title":"Selective protein kinase C inhibitors and their applications","volume":"3","author":"Shen","year":"2003","journal-title":"Curr. Drug Targets Cardiovasc. Hematol. Disord."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.mvr.2010.01.003","article-title":"A PKC-\u03b2 inhibitor treatment reverses cardiac microvascular barrier dysfunction in diabetic rats","volume":"80","author":"Wei","year":"2010","journal-title":"Microvasc. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1167\/iovs.61.5.36","article-title":"Role of arginase in selective impairment of endothelium-dependent nitric oxide synthase-mediated dilation of retinal arterioles during early diabetes","volume":"61","author":"Hein","year":"2020","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1046\/j.1523-1755.1999.00229.x","article-title":"Increased NAD(P)H oxidase-mediated superoxide production in renovascular hypertension: Evidence for an involvement of protein kinase C","volume":"55","author":"Heitzer","year":"1999","journal-title":"Kidney Int."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"H989","DOI":"10.1152\/ajpheart.00416.2012","article-title":"Diabetes-induced increased oxidative stress in cardiomyocytes is sustained by a positive feedback loop involving Rho kinase and PKC\u03b22","volume":"303","author":"Soliman","year":"2012","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1161\/01.ATV.0000196651.64776.51","article-title":"Coronary artery superoxide production and nox isoform expression in human coronary artery disease","volume":"26","author":"Guzik","year":"2006","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_59","first-page":"24","article-title":"Activation of protein kinase C pathway contributes to hydrogen peroxide-induced increase in endothelial permeability","volume":"67","author":"Goligorsky","year":"1992","journal-title":"Lab. Investig. J. Tech. Methods Pathol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1161\/01.HYP.32.6.1003","article-title":"Reactive oxygen species are critical in the oleic acid-mediated mitogenic signaling pathway in vascular smooth muscle cells","volume":"32","author":"Lu","year":"1998","journal-title":"Hypertension"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.2337\/diabetes.49.11.1939","article-title":"High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C-dependent activation of NAD(P)H oxidase in cultured vascular cells","volume":"49","author":"Inoguchi","year":"2000","journal-title":"Diabetes"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/0162-3109(90)90023-8","article-title":"Dissimilarities in superoxide anion production by human neutrophils stimulated by phorbol myristate acetate or phorbol dibutyrate","volume":"19","author":"Gaudry","year":"1990","journal-title":"Immunopharmacology"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"19417","DOI":"10.3390\/ijms151119417","article-title":"Obligatory role of intraluminal O2- in acute endothelin-1 and angiotensin II signaling to mediate endothelial dysfunction and MAPK activation in guinea-pig hearts","volume":"15","author":"Wojtera","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1161\/01.ATV.0000201932.32678.7e","article-title":"TNF-\u03b1 contributes to endothelial dysfunction in ischemia\/reperfusion injury","volume":"26","author":"Zhang","year":"2006","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1016\/j.freeradbiomed.2005.06.004","article-title":"Oxypurinol improves coronary and peripheral endothelial function in patients with coronary artery disease","volume":"39","author":"Baldus","year":"2005","journal-title":"Free Radic. Biol. Med."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Chen, Y.L., Ren, Y., Rosa, R.H., Kuo, L., and Hein, T.W. (2021, August 20). Contributions of sodium-hydrogen exchanger-1 and mitogen-activated protein kinases to enhanced retinal venular constriction to endothelin-1 in diabetes, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/34353852\/.","DOI":"10.2337\/db20-0889"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1089\/ars.2010.3614","article-title":"Redox regulation of protein kinases as a modulator of vascular function","volume":"15","author":"Knock","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1139\/Y09-004","article-title":"Role of protein kinase C \u03b22 activation in TNF-\u03b1-induced human vascular endothelial cell apoptosis","volume":"87","author":"Wang","year":"2009","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"L872","DOI":"10.1152\/ajplung.00199.2010","article-title":"Rho kinase modulates postnatal adaptation of the pulmonary circulation through separate effects on pulmonary artery endothelial and smooth muscle cells","volume":"299","author":"Alvira","year":"2010","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"165","DOI":"10.4103\/0975-3583.74258","article-title":"The role of RhoA\/Rho kinase pathway in endothelial dysfunction","volume":"1","author":"Yao","year":"2010","journal-title":"J. Cardiovasc. Dis. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1161\/CIRCRESAHA.115.306532","article-title":"RhoA\/Rho-kinase in the cardiovascular system","volume":"118","author":"Shimokawa","year":"2016","journal-title":"Circ. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.freeradbiomed.2018.04.580","article-title":"Anagliptin inhibits neointimal hyperplasia after balloon injury via endothelial cell-specific modulation of SOD-1\/RhoA\/JNK signaling in the arterial wall","volume":"121","author":"Li","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.1161\/01.ATV.0000175749.41799.9b","article-title":"Signal-crosstalk between Rho\/ROCK and c-Jun NH2-terminal kinase mediates migration of vascular smooth muscle cells stimulated by angiotensin II","volume":"25","author":"Ohtsu","year":"2005","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/bs.apha.2016.06.002","article-title":"Protein kinase C as regulator of vascular smooth muscle function and potential target in vascular disorders","volume":"78","author":"Ringvold","year":"2017","journal-title":"Adv. Pharmacol."},{"key":"ref_75","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_76","doi-asserted-by":"crossref","first-page":"2328","DOI":"10.1096\/fj.03-0115fje","article-title":"Ischemia-reperfusion selectively impairs nitric oxide-mediated dilation in coronary arterioles: Counteracting role of arginase","volume":"17","author":"Hein","year":"2003","journal-title":"FASEB J."},{"key":"ref_77","first-page":"H1558","article-title":"Myogenic activity in isolated subepicardial and subendocardial coronary arterioles","volume":"255","author":"Kuo","year":"1988","journal-title":"Am. J. Physiol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1161\/01.RES.69.3.561","article-title":"Microvascular pressures and resistances in the left ventricular subepicardium and subendocardium","volume":"69","author":"Chilian","year":"1991","journal-title":"Circ. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2904","DOI":"10.1167\/iovs.12-9542","article-title":"Constriction of retinal arterioles to endothelin-1: Requisite role of rho kinase independent of protein kinase C and L-type calcium channels","volume":"53","author":"Potts","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2408240","DOI":"10.1155\/2020\/2408240","article-title":"Selective inhibition of PKC\u03b22 restores ischemic postconditioning-mediated cardioprotection by modulating autophagy in diabetic rats","volume":"2020","author":"Wang","year":"2020","journal-title":"J. Diabetes Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1161\/CIRCRESAHA.110.237636","article-title":"H2O2 is the transferrable factor mediating flow-induced dilation in human coronary arterioles","volume":"108","author":"Liu","year":"2011","journal-title":"Circ. Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1161\/01.RES.0000056759.53828.2C","article-title":"Divergent roles of angiotensin II AT1 and AT2 receptors in modulating coronary microvascular function","volume":"92","author":"Zhang","year":"2003","journal-title":"Circ. Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1161\/01.ATV.0000258416.47953.9a","article-title":"Exercise training restores coronary arteriolar dilation to NOS activation distal to coronary artery occlusion: Role of hydrogen peroxide","volume":"27","author":"Thengchaisri","year":"2007","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1161\/CIRCRESAHA.114.301763","article-title":"Selective activation of LOX-1 mediates C-reactive protein evoked endothelial vasodilator dysfunction in coronary arterioles","volume":"114","author":"Hein","year":"2014","journal-title":"Circ. Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/18\/9763\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:59:39Z","timestamp":1760165979000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/18\/9763"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,9]]},"references-count":84,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["ijms22189763"],"URL":"https:\/\/doi.org\/10.3390\/ijms22189763","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,9]]}}}