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The aim of this review is to highlight the cardioprotective potential of urocortins and corticotropin-releasing hormone (CRH) and their signaling. It has been documented that urocortins and CRH reduce ischemic and reperfusion (I\/R) injury, prevent reperfusion ventricular tachycardia and fibrillation, and improve cardiac contractility during reperfusion. Urocortin-induced increase in cardiac tolerance to I\/R depends mainly on the activation of corticotropin-releasing hormone receptor-2 (CRHR2) and its downstream pathways including tyrosine kinase Src, protein kinase A and C (PKA, PKC\u03b5) and extracellular signal-regulated kinase (ERK1\/2). It was discussed the possibility of the involvement of interleukin-6, Janus kinase-2 and signal transducer and activator of transcription 3 (STAT3) and microRNAs in the cardioprotective effect of urocortins. Additionally, phospholipase-A2 inhibition, mitochondrial permeability transition pore (MPT-pore) blockade and suppression of apoptosis are involved in urocortin-elicited cardioprotection. Chronic administration of urocortin-2 prevents the development of postinfarction cardiac remodeling. Urocortin possesses vasoprotective and vasodilator effect; the former is mediated by PKC activation and prevents an impairment of endothelium-dependent coronary vasodilation after I\/R in the isolated heart, while the latter includes both cAMP and cGMP signaling and its downstream targets. As CRHR2 is expressed by both cardiomyocytes and vascular endothelial cells. Urocortins mediate both endothelium-dependent and -independent relaxation of coronary arteries.<\/jats:p>","DOI":"10.1177\/1074248420985301","type":"journal-article","created":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T13:27:58Z","timestamp":1628170078000},"page":"575-584","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["Cardioprotective and Vasoprotective Effects of Corticotropin-Releasing Hormone and Urocortins: Receptors and Signaling"],"prefix":"10.1177","volume":"26","author":[{"given":"Sergey V.","family":"Popov","sequence":"first","affiliation":[{"name":"Laboratory of Experimental Cardiology, Cardiology Research Institute, Tomsk National Research Medical Center of the RAS, Tomsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ekaterina S.","family":"Prokudina","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Cardiology, Cardiology Research Institute, Tomsk National Research Medical Center of the RAS, Tomsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander V.","family":"Mukhomedzyanov","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Cardiology, Cardiology Research Institute, Tomsk National Research Medical Center of the RAS, Tomsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia V.","family":"Naryzhnaya","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Cardiology, Cardiology Research Institute, Tomsk National Research Medical Center of the RAS, Tomsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huijie","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Physiology, Hebei Medical University, Shijiazhuang, Hebei Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jitka M.","family":"Zurmanova","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Science, Charles University, Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter F. 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