{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T17:53:05Z","timestamp":1784829185967,"version":"3.55.0"},"reference-count":44,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T00:00:00Z","timestamp":1638144000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Persistent cardiac Ca<jats:sup>2+<\/jats:sup>\/calmodulin\u2010dependent Kinase II (CaMKII) activation was considered to promote heart failure (HF) development, some studies believed that CaMKII was a target for therapy of HF. However, CaMKII was an important mediator for the ischaemia\u2010induced coronary angiogenesis, and new evidence confirmed that angiogenesis inhibited cardiac remodelling and improved heart function, and some conditions which impaired angiogenesis aggravated ventricular remodelling. This study aimed to investigate the roles and the underlying mechanisms of CaMKII inhibitor in cardiac remodelling. First, we induced cardiac remodelling rat model by ISO, pre\u2010treated by CaMKII inhibitor KN\u201093, evaluated heart function by echocardiography measurements, and performed HE staining, Masson staining, Tunel staining, Western blot and RT\u2010PCR to test cardiac remodelling and myocardial microvessel density; we also observed ultrastructure of cardiac tissue with transmission electron microscope. Second, we cultured HUVECs, pre\u2010treated by ISO and KN\u201093, detected cell proliferation, migration, tubule formation and apoptosis, and carried out Western blot to determine the expression of NOX2, NOX4, VEGF, VEGFR2, p\u2010VEGFR2 and STAT3; mtROS level was also measured. In vivo, we found KN\u201093\u00a0severely reduced myocardial microvessel density, caused apoptosis of vascular endothelial cells, enhanced cardiac hypertrophy, myocardial apoptosis, collagen deposition, aggravated the deterioration of myocardial ultrastructure and heart function. In vitro, KN\u201093 inhibited HUVECs proliferation, migration and tubule formation, and promoted apoptosis of HUVECs. The expression of NOX2, NOX4, p\u2010VEGFR2 and STAT3 were down\u2010regulated by KN\u201093; mtROS level was severely reduced by KN\u201093. We concluded that KN\u201093 impaired angiogenesis and aggravated cardiac remodelling and heart failure via inhibiting NOX2\/mtROS\/p\u2010VEGFR2 and STAT3 pathways.<\/jats:p>","DOI":"10.1111\/jcmm.17081","type":"journal-article","created":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T16:33:24Z","timestamp":1638290004000},"page":"312-325","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["CaMKII inhibitor KN\u201093 impaired angiogenesis and aggravated cardiac remodelling and heart failure via inhibiting NOX2\/mtROS\/p\u2010VEGFR2 and STAT3 pathways"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6332-0920","authenticated-orcid":false,"given":"Yajuan","family":"Ni","sequence":"first","affiliation":[{"name":"Department of Cardiology The Second Affiliated Hospital of Xi\u2019an Jiaotong University Xi'an 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