Bone marrow stromal cell transplantation combined with angiotensin-converting enzyme inhibitor treatment in rat with acute myocardial infarction and the role of insulin-like growth factor-1

Abstract

Background aims. We investigated bone marrow stromal cell (BMSC) transplantation combined with angiotensin-converting enzyme inhibitor (ACEI) treatment in acute myocardial infarction (AMI) and the role of insulin-like growth factor-1 (IGF-1). Methods. AMI models were established in Sprague–Dawley rats by ligation of the left anterior descending coronary artery and grouped into blank control (BC), ACEI treatment (ACEI), BMSC transplantation (BMSC) and BMSC transplantation plus ACEI (combined). Perindopril (2.5 mg/kg) was administered by gavage to ACEI and combined groups from the day after AMI. BMSC (2 × 10⁸) were injected into the border of the MI area a week later in the BMSC and combined groups. Results. After 4 weeks, hemodynamics in the BMSC and combined groups were significantly improved (P < 0.05 versus BC), with the greatest improvement in the combined group (P < 0.05). In addition, an increased number of BMSC survived in the combined group (P < 0.05 versus BMSC). A proportion of BMSC was positive for troponin T, as detected by immunofluorescence. The number of apoptotic cardiomyocytes was decreased in the BMSC and ACEI groups, and even further in the combined group (P < 0.05). IGF-1 expression was up-regulated in the BMSC and combined groups (P < 0.05 versus BC), but not in the ACEI group. B cell lymphoma-2 (Bcl-2) expression was up-regulated in the ACEI, BMSC and combined groups, with the highest expression in the combined group (P < 0.05). Conclusions. Our results show that BMSC engrafted in AMI can survive well and secrete IGF-1 and preserve cardiac function significantly. These data suggest that BMSC transplantation inhibits apoptosis of cardiomyocytes by up-regulation of Bcl-2 expression in the myocardium, and this effect might be sensitized by ACEI.

Key Words::

• acute myocardial infarction
• angiotensin-converting enzyme inhibitor
• bone marrow stromal cells
• insulin-like growth factor-1

Acknowledgments

This study was supported by the Natural Science Foundation of Guangdong Province, China (number 8151008901000157), Scientific Research Fund of Guangdong, China (number 2008B030301045, 2009A030301004, 2011B031800021), and Medical Scientific Research Grant of Health Ministry of Guangdong province, China (number B2011310).

Conflict of interest: none to declare.