Abstract

BackgroundThe effects of atorvastatin on SDF-1α expression under acute myocardial infarction (AMI) are still unclear. Therefore, our present study is to investigate the roles and mechanisms of atorvastatin treatment on SDF-1α expression in rats with AMI.MethodsMale Sprague–Dawley rats were underwent permanent coronary artery ligation and randomly assigned into four groups as follow: blank control (B), atorvastatin (A), atorvastatin plus L-NAME (A+L-NAME), and atorvastatin plus AMD3100 (A+AMD3100). Rats underwent similar procedure but without ligation were used as group sham operated (S). Atorvastatin (10mg/Kg/d body weight) was administrated by gavage to rats in three atorvastatin treated groups, and L-NAME (40mg/Kg/d body weight) or AMD3100 (5mg/Kg/d body weight) was given to group A+L-NAME or A+AMD3100, respectively.ResultsComparing with group B, NO production, SDF-1α and CXCR4 expression were significantly up-regulated in three atorvastatin treated groups at the seventh day. However, the increments of SDF-1α and CXCR4 expression in group A+L-NAME were reduced when NO production was inhibited by L-NAME. Anti-inflammatory and anti-apoptotic effects of atorvastatin were offset either by decrease of SDF-1α and CXCR4 expression (by L-NAME) or blockage of SDF-1α coupling with CXCR4 (by AMD3100). Expression of STAT3, a cardioprotective factor mediating SDF-1α/CXCR4 axis induced cardiac protection, was up-regulated most significantly in group A. The effects of atorvastatin therapy on cardiac function were also abrogated either when SDF-1α and CXCR4 expression was diminished or the coupling of SDF-1α with CXCR4 was blocked.ConclusionSDF-1α upregulation by atorvastatin in rats with AMI was, at least partially, via the eNOS/NO dependent pathway, and SDF-1α upregulation and SDF-1α coupling with CXCR4 conferred anti-inflammatory and anti-apoptotic effects under AMI setting which we speculated that ultimately contributed to cardiac function improvement.

Highlights

  • The effects of atorvastatin on SDF-1α expression under acute myocardial infarction (AMI) are still unclear

  • Expression of endothelial nitric oxide synthase (eNOS) and p-eNOS in myocardium was up-regulated by atorvastatin administration As shown in Figure 1, seven days after AMI, comparing with group B, eNOS and p-eNOS were significantly increased in all three atorvastatin therapy groups (P

  • nitric oxide (NO) production in both group A and group A+AMD3100 was significantly increased (P

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Summary

Introduction

The effects of atorvastatin on SDF-1α expression under acute myocardial infarction (AMI) are still unclear. Our present study is to investigate the roles and mechanisms of atorvastatin treatment on SDF-1α expression in rats with AMI. The outcomes are striking and shed promising lights on SDF-1α potentially therapeutic efficacy on ischemic diseases. Notwithstanding, those novel genetic approaches seem infeasible in clinical practice at present time. It is warranted and necessitated to investigate whether commonly used medications have potential to up-regulate SDF-1α expression after AMI. We hypothesized that increase of SDF-1α might be, at least partially, attributable to eNOS upregulation and NO production by statins treatment, and the reciprocal coupling of SDF-1α with CXCR4 might be another novel mechanism by which statins confer its pleiotropic effects on cardiovascular diseases

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