{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T23:29:29Z","timestamp":1785540569034,"version":"3.56.0"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:sec><jats:title>Objective\u2014<\/jats:title><jats:p>Stimulation of cardiac \u03b1<jats:sub>1A<\/jats:sub>-adrenergic receptors (\u03b1<jats:sub>1A<\/jats:sub>-AR) has been proposed for treatment of heart failure, since it increases myocardial contractility. We investigated a different mechanism, induction of angiogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Approach and Results\u2014<\/jats:title><jats:p>Four to 6 weeks after permanent coronary artery occlusion, transgenic rats with cardiomyocyte-specific \u03b1<jats:sub>1A<\/jats:sub>-adrenergic receptor overexpression had less remodeling than their nontransgenic littermates, with less fibrosis, hypertrophy and lung weight, and preserved left ventricular ejection fraction and wall stress (all<jats:italic>P<\/jats:italic>&lt;0.05). Coronary blood flow, measured with microspheres, increased in the infarct zone in transgenic rats compared with nontransgenic littermates (1.4\u00b10.2 versus 0.5\u00b10.08 mL min<jats:sup>\u22121<\/jats:sup>g<jats:sup>\u22121<\/jats:sup>;<jats:italic>P<\/jats:italic>&lt;0.05), which is consistent with angiogenesis, as reflected by a 20% increase in capillary density in the zone adjacent to the infarct. The question arose, how does transgenic overexpression of a gene in cardiomyocytes induce angiogenesis? We identified a paracrine mechanism, whereby vascular endothelial growth factor-A mRNA and protein were increased in isolated transgenic cardiomyocytes and also by nontransgenic littermate cardiomyocytes treated with an \u03b1<jats:sub>1A<\/jats:sub>-agonist, resulting in angiogenesis. Conditioned medium from cultured cardiomyocytes treated with an \u03b1<jats:sub>1A<\/jats:sub>agonist enhanced human umbilical vein endothelial cell tubule formation, which was blocked by an anti\u2013vascular endothelial growth factor-A antibody. Moreover, improved cardiac function, blood flow, and increased capillary density after chronic coronary artery occlusion in transgenic rats were blocked by either a mitogen ERK kinase (MEK) or a vascular endothelial growth factor-A inhibitor.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion\u2014<\/jats:title><jats:p>Cardiomyocyte-specific overexpression of the \u03b1<jats:sub>1A<\/jats:sub>-adrenergic receptors resulted in enhanced MEK-dependent cardiomyocyte vascular endothelial growth factor-A expression, which stimulates angiogenesis via a paracrine mechanism involving heterocellular cardiomyocyte\/endothelial cell signaling, protecting against remodeling and heart failure after chronic coronary artery occlusion.<\/jats:p><\/jats:sec>","DOI":"10.1161\/atvbaha.115.305919","type":"journal-article","created":{"date-parts":[[2015,9,4]],"date-time":"2015-09-04T03:19:15Z","timestamp":1441336755000},"page":"2451-2459","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":33,"title":["Overexpression of Cardiomyocyte \u03b1<sub>1A<\/sub>-Adrenergic Receptors Attenuates Postinfarct Remodeling by Inducing Angiogenesis Through Heterocellular Signaling"],"prefix":"10.1161","volume":"35","author":[{"given":"Xin","family":"Zhao","sequence":"first","affiliation":[{"name":"From the Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, Rutgers-New Jersey Medical School, Newark (X.Z., R.P., D.E.V., S.F.V.); and Victor Chang Cardiac Research Institute and Faculty of Medicine and Life Sciences, University of New South Wales, Sydney, New South Wales, Australia (P.B., D.M.B., R.M.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Poornima","family":"Balaji","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, Rutgers-New Jersey Medical School, Newark (X.Z., R.P., D.E.V., S.F.V.); and Victor Chang Cardiac Research Institute and Faculty of Medicine and Life Sciences, University of New South Wales, Sydney, New South Wales, Australia (P.B., D.M.B., R.M.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Pachon","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, Rutgers-New Jersey Medical School, Newark (X.Z., R.P., D.E.V., S.F.V.); and Victor Chang Cardiac Research Institute and Faculty of Medicine and Life Sciences, University of New South Wales, Sydney, New South Wales, Australia (P.B., D.M.B., R.M.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniella M.","family":"Beniamen","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, Rutgers-New Jersey Medical School, Newark (X.Z., R.P., D.E.V., S.F.V.); 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