Abstract 14672: A Pivotal Role of Synthetic Smooth Muscle Cells Activated by Hepatocyte Growth Factor in Extracellular Matrix Modulation-Related Functional Recovery Post-Cell Sheet Transplantation in a Rat Chronic Myocardial Infarction Model
Background: Transplantation of autologous skeletal myoblast cell (SMB)-sheet has been shown to upregulate intramyocardial expression of various factors including hepatocyte growth factor (HGF) and consequently recover cardiac function of chronic myocardial infarction (MI) heart, though underlying mechanisms are not fully understood. It is known that synthetic (Syn)-smooth muscle cell (SMC), which is phenotypically changed from contractile-SMC (Con-SMC), is the major player to regulate extracellular matrix (ECM) in the heart. We herein hypothesized that upregulated HGF in the myocardium after SMB-sheet transplantation may induce accumulation of Syn-SMCs to modulate ECM and to yield functional recovery.
Methods: At 2 weeks after left coronary artery ligation in the Lewis rat, transplantation of Lewis rat SMB sheet on surface of the heart or sham operation was performed with or without intraperitoneal injection of neutralization antibody against HGF.
Results: Echocardiographically, ejection fraction was recovered at 7 days after the treatment in the SMB only (SMB) group (46±2% to 49±3%), but not in the SMB plus anti-HGF (SMBH) (46±2% to 39±3%), the sham (46±4 to 42±2%) or the sham plus anti-HGF (shamH) (46±4% to 40±4%). Interestingly, the SMB roup displayed accumulation of both Syn- and Con-SMCs around endothelium and in the ECM of the infarct border area, whereas only Con-SMCs were seen in the other groups at 7 days. In addition, collagen fibers in the infarct-border area was significantly less accumulated in the SMB group (12±2%) than the SMBH group (31±5%). Moreover, expression of elastin, fibronectin and HGF were significantly upregulated in the SMB by real-time PCR. Consistently, primary SMCs treated with recombinant HGF exhibited increase of elastin, whereas those treated with anti-HGF antibody exhibited decrease of elastin, in vitro. CD31-positve capillary number in the infarct-border area was significantly greater in the SMB group (1,024±197/mm2) than the other groups, such as the SMBH (726±151/mm2), the sham (596±112/mm2) or the shamH (685±166/mm2) groups.
Conclusion: HGF and HGF-activating Syn-SMC play a pivotal role in ECM modulation-associated functional recovery with after SMB sheet transplantation for chronic MI rat heart.
Author Disclosures: M. Shiozaki: None. S. Miyagawa: None. S. Fukushima: None. D. Yoshioka: None. A. Saito: None. Y. Sakai: None. K. Matsumoto: None. Y. Sawa: None.
- © 2016 by American Heart Association, Inc.