{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T20:41:58Z","timestamp":1776890518823,"version":"3.51.2"},"reference-count":37,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2012,2,15]]},"abstract":"<jats:p> The angiopoietins\/Tie-2 system is essential for the maintenance of vascular integrity and angiogenesis. The functional role of angiopoietin-2 (Ang-2) in the regulation of angiogenesis is dependent on other growth factors such as VEGF and a given physiopathological conditions. This study investigates the potential role of Ang-2 in myocardial angiogenesis and fibrosis formation in the diabetic db\/db mouse. Diabetic db\/db mice received intramyocardial administration of either adenovirus Ang-2 (Ad-CMV-Ang-2) or Ad-\u03b2-gal. The levels of Tie-2, VEGF, caspase-3, Wnt7b, fibroblast-specific protein-1 (FSP-1), and adhesion molecules (ICAM-1 and VCAM-1) expression were measured. Apoptosis, capillary density, and cardiac fibrosis were also analyzed in the db\/db mouse hearts. Overexpression of Ang-2 suppressed Tie-2 and VEGF expression in db\/db mouse hearts together with significant upregulation of Wnt7b expression. Overexpression of Ang-2 also sensitizes ICAM-1 and VCAM-1 expression in db\/db mouse hearts. Immunohistochemical analysis revealed that overexpression of Ang-2 resulted in a gradual apoptosis as well as interstitial fibrosis formation, these leading to a significant loss of capillary density. Data from these studies were confirmed in cultured mouse heart microvascular endothelial cells (MHMEC) exposed to excessive Ang-2. Exposure of MHMEC to Ang-2 resulted in increased caspase-3 activity and endothelial apoptosis. Knockdown of Ang-2 attenuated high glucose-induced endothelial cell apoptosis. Further, counterbalance of Ang-2 by overexpression of Ang-1 reversed loss of capillary density and fibrosis formation in db\/db mouse hearts. Our data demonstrate that Ang-2 increases endothelial apoptosis, sensitizes myocardial microvascular inflammation, and promotes cardiac fibrosis and thus contributes to loss of capillary density in diabetic diseases. <\/jats:p>","DOI":"10.1152\/ajpheart.00866.2011","type":"journal-article","created":{"date-parts":[[2011,12,17]],"date-time":"2011-12-17T03:41:38Z","timestamp":1324093298000},"page":"H1003-H1012","source":"Crossref","is-referenced-by-count":62,"title":["Overexpression of angiopoietin-2 impairs myocardial angiogenesis and exacerbates cardiac fibrosis in the diabetic <i>db\/db<\/i> mouse model"],"prefix":"10.1152","volume":"302","author":[{"given":"Jian-Xiong","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heng","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi; 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