title: Testosterone replacement therapy promotes angiogenesis after acute myocardial infarction by enhancing expression of cytokines HIF-1a, SDF-1a and VEGF.
abstract: In order to investigate the effects of testosterone-replacement therapy on peripheral blood stem cells and angiogenesis after acute myocardial infarction, a castrated rat acute myocardial infarction model was established by ligation of the left anterior descending coronary followed by treatment with testosterone. CD34(+) cells in myocardium and in peripheral blood after 1 and 3 days were measured by immunohistochemistry and flow cytometry, respectively. In the early phase of acute myocardial infarction, the expression levels of hypoxia-inducible factor 1a (HIF-1a), stromal cell-derived factor 1a (SDF-1a) and vascular endothelium growth factor (VEGF) in ischemic myocardium were determined by real time RT-PCR and immunohistochemistry, respectively. Infarct size, cardiomyocyte apoptosis, capillary density and cardiac function were assessed after 28 days. These results showed that the number of CD34(+) cells in the peripheral blood and in myocardium was significantly decreased in castrated rats, and the early expression levels of HIF-1a, SDF-1a and VEGF in the myocardium were also decreased. Furthermore, reduced capillary density, worsened cardiac function, increased infarct size and cardiomyocyte apoptosis at 28 days post-infarction were found in castrated rats. But these adverse effects could be reversed by testosterone-replacement therapy. These findings suggested that testosterone can increase the mobilization and homing of CD34(+) cells into the ischemic myocardium and further promote neoangiogenesis after myocardial infarction. The pro-angiogenesis effect of testosterone-replacement therapy is associated with the enhanced expression of HIF-1a, SDF-1a and VEGF in myocardium after myocardial infarction.
authors.affiliation: Department of Cardiovascular Medicine, First Affiliated Hospital, Harbin Medical University, Harbin 150001, China.
authors.forename: Yeping
authors.initials: Y
authors.lastname: Chen
authors.forename: Lu
authors.initials: L
authors.lastname: Fu
authors.forename: Ying
authors.initials: Y
authors.lastname: Han
authors.forename: Yueqiu
authors.initials: Y
authors.lastname: Teng
authors.forename: Junfeng
authors.initials: J
authors.lastname: Sun
authors.forename: Rongsheng
authors.initials: R
authors.lastname: Xie
authors.forename: Junxian
authors.initials: J
authors.lastname: Cao
mesh_terms: D000208:Acute Disease; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002196:Capillaries / Q000187:drug effects / Q000378:metabolism; D002369:Castration; D054377:Chemokine CXCL12 / Q000235:genetics; D004967:Estrogens / Q000097:blood; D005786:Gene Expression Regulation / Q000187:drug effects*; D020249:Hormone Replacement Therapy; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics; D008297:Male; D009203:Myocardial Infarction / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013739:Testosterone / Q000097:blood / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: D018952:Antigens, CD34; D054377:Chemokine CXCL12; D004967:Estrogens; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D013739:Testosterone