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.
Highlights
Diabetes mellitus (DM) is an independent predictor of adverse outcomes in patients with acute myocardial infarction (AMI) [1, 2]
fasting blood glucose (FBG) and postprandial blood glucose (PBG) were both raised after STZ injection, whilst insulin tolerance test (ITT) showed a delayed reduction of plasma glucose in diabetic rats (Figure 1), and insulin sensitivity index (ISI) was reduced, all indicating establishment of diabetes and insulin
In order to characterize the effect of amlodipine and perindopril on cardiac systolic function and cardiac remodeling, we examined expression of B-type natriuretic peptide (BNP) by Real-time polymerase chain reaction (RT-PCR)
Summary
Diabetes mellitus (DM) is an independent predictor of adverse outcomes in patients with acute myocardial infarction (AMI) [1, 2]. ACE inhibitors, which are widely used in patients with cardiovascular disease, have been demonstrated to exert beneficial effects on EPC biology [17,18,19] They can enhance the release of NO through activating the protein kinase B (Akt)/endothelial NO synthase (eNOS) pathway [20, 21], and NO in turn has an essential role in mobilization of EPCs, an event which is required for myocardial neovascularization and survival after AMI [22, 23]. Based on these considerations, we wished to examine whether amlodipine may influence CHD development and recovery through NO-mediated EPC mobilization, in the same way as ACE inhibitors
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