Syndecan-4 over-expression preserves cardiac function in a rat model of myocardial infarction.

Abstract

Syndecan-4 (synd4) is a heparan sulfate proteoglycan, involved in repair following tissue damage, through modulating neovascularization and inflammation. In acute myocardial infarction its myocardial expression is up-regulated in a time-dependent manner, and in synd4-deficient mice severe cardiac dysfunction and abnormal remodeling are observed following induction of myocardial infarction. Here we explored the therapeutic potential of sustained synd4 over-expression in the context of myocardial infarction. Adenovirus containing the synd4 gene (Ad-synd4), or corresponding control adenovirus (Ad-null), was administered intramyocardially in rats immediately after induction of myocardial infarction. Cardiac function was ascertained by echocardiography, hemodynamic assessment and brain natriuretic peptide level 28 days post-intervention. Hearts were excised for molecular and histological analyses at predetermined time points. We observed reduced mortality and improved cardiac function post-myocardial infarction in the Ad-synd4 as compared to the Ad-null group, with associated attenuation of cardiac remodeling, less myocyte loss and reduced fibrosis. Additionally, the Ad-synd4 group exhibited endothelial cell activation and increased angiogenesis and arteriogenesis in the myocardium. The Ad-synd4 group also showed evidence of reduced myocardial inflammation as compared with the Ad-null group, with reduced inflammatory cell (CD45+) and myofibroblast (α-SMA+) infiltration as well as suppressed collagen III deposition and iNOS expression. Our results suggest that sustained synd4 over-expression in the myocardium is of therapeutic benefit following experimental myocardial infarction, through inducing neovascularization, suppressing tissue inflammation and fibrosis, with resultant improvements in cardiac function and remodeling.

• Authors: Jun Xie, Jingjing Wang, Ruotian Li, Qin Dai, Yonghong Yong, Bing Zong, Yunxia Xu, Erguang Li, Albert Ferro, Biao Xu
• Journal: Journal of molecular and cellular cardiology (J Mol Cell Cardiol) Vol. 53 Issue 2 Pg. 250-8 (Aug 2012) ISSN: 1095-8584 [Electronic] England
• PMID: 22561100 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Syndecan-4

Topics

• Animals
• Cells, Cultured
• Disease Models, Animal
• Humans
• Male
• Myocardial Infarction (genetics, metabolism, therapy)
• Myocytes, Cardiac (cytology, metabolism)
• Rats
• Rats, Sprague-Dawley
• Syndecan-4 (genetics, metabolism)