title: Amlodipine Ameliorates Ischemia-Induced Neovascularization in Diabetic Rats through Endothelial Progenitor Cell Mobilization.
abstract: Objectives. We investigated whether amlodipine could improve angiogenic responses in a diabetic rat model of acute myocardial infarction (AMI) through improving bone marrow endothelial progenitor cell (EPC) mobilization, in the same way as angiotensin converting enzyme inhibitors. Methods. After induction of AMI by coronary artery ligation, diabetic rats were randomly assigned to receive perindopril (2 mgkg(-1) day(-1)), amlodipine (2.5 mgkg(-1) day(-1)), or vehicle by gavage (n = 20 per group). Circulating EPC counts before ligation and on days 1, 3, 5, 7, 14, and 28 after AMI were measured in each group. Microvessel density, cardiac function, and cardiac remodeling were assessed 4 weeks after treatment. The signaling pathway related to EPC mobilization was also measured. Results. Circulating EPC count in amlodipine- and perindopril-treated rats peaked at day 7, to an obvious higher level than the control group peak which was reached earlier (at day 5). Rats treated with amlodipine showed improved postischemia neovascularization and cardiac function, together with reduced cardiac remodeling, decreased interstitial fibrosis, and cardiomyocyte apoptosis. Amlodipine treatment also increased cardiac SDF-1/CXCR4 expression and gave rise to activation of VEGF/Akt/eNOS signaling in bone marrow. Conclusions. Amlodipine promotes neovascularization by improving EPC mobilization from bone marrow in diabetic rats after AMI, and activation of VEGF/Akt/eNOS signaling may in part contribute to this.
authors.affiliation: Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China; Department of Cardiology, Affiliated Drum Tower Hospital, Nanjing University Medical School, 321 Zhongshan Road, Nanjing 210008, China.
authors.forename: Jiayin
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Cardiology, Affiliated Drum Tower Hospital, Nanjing University Medical School, 321 Zhongshan Road, Nanjing 210008, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xie
authors.affiliation: Department of Cardiology, Affiliated Drum Tower Hospital, Nanjing University Medical School, 321 Zhongshan Road, Nanjing 210008, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Kang
authors.affiliation: Cardiovascular Division, British Heart Foundation Centre of Research Excellence, King's College London, 150 Stamford Street, London SE1 9NH, UK.
authors.forename: Albert
authors.initials: A
authors.lastname: Ferro
authors.affiliation: Department of Cardiology, Hospital of Nanjing Municipal Authorities, Nanjing 210008, China.
authors.forename: Li
authors.initials: L
authors.lastname: Dong
authors.affiliation: Department of Cardiology, Affiliated Drum Tower Hospital, Nanjing University Medical School, 321 Zhongshan Road, Nanjing 210008, China.
authors.forename: Biao
authors.initials: B
authors.lastname: Xu
mesh_terms: D017311:Amlodipine / Q000008:administration & dosage*; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D016207:Cytokines / Q000276:immunology; D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D066026:Endothelial Progenitor Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
chemical_list: D016207:Cytokines; D017311:Amlodipine