Sdc1 overexpression inhibits the p38 MAPK pathway and lessens fibrotic ventricular remodeling in MI rats.

Abstract

Expression of the proteoglycan syndecan-1 (Sdc1) is increased in rats with myocardial infarction (MI). This study investigated the effects of Sdc1 overexpression on ventricular remodeling and cardiac function in MI and explored the possible mechanism through in vivo transfection of rats with recombinant adenovirus-carrying rat Sdc1 cDNA. Sprague-Dawley rats (n = 48) underwent intramyocardial injection in the marginal zone of the infarcted area immediately after ligation of the left anterior descending artery. The rats were divided into four groups according to the solution injected: MI Ad-GFP-Sdc1 transfection group, MI Ad-GFP control group, MI saline group, and sham operation group. Cardiac function and collagen expression of each group were examined, and the roles of inflammation, apoptosis, and p38 MAKP signal transduction pathway were investigated. Compared with the rats in the sham operation group, ventricular weight and collagen content increased in MI rats, and cardiac function declined. Substantial inflammatory cell infiltration was seen in the marginal zone of the infarction area, and a great number of myocardial cells were apoptotic. The p38 MAPK signaling pathway was clearly activated. Rats in the MI Ad-GFP-Sdc1 transfection group showed decreased ventricular weight, reduced collagen synthesis, and significant improvement of ventricular remodeling and cardiac function. Post-MI inflammatory cell infiltration and apoptosis was reduced, and the p38 MAPK signaling pathway was inhibited. Overexpression of Sdc1 can improve post-MI ventricular remodeling, and it is possible that the improvement is achieved through reducing apoptosis and suppressing inflammatory response and through the p38 MAPK signal transduction pathway.

• Authors: Juan Lei, Shengneng Xue, Wei Wu, Shuxian Zhou, Yuling Zhang, Guiyi Yuan, Jingfeng Wang
• Journal: Inflammation (Inflammation) Vol. 36 Issue 3 Pg. 603-15 (Jun 2013) ISSN: 1573-2576 [Electronic] United States
• PMID: 23264165 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Sdc1 protein, rat
• Syndecan-1
• Green Fluorescent Proteins
• p38 Mitogen-Activated Protein Kinases

Topics

• Adenoviridae (genetics)
• Animals
• Apoptosis
• Fibrosis
• Gene Transfer Techniques
• Genetic Vectors
• Green Fluorescent Proteins (genetics)
• Inflammation (immunology)
• MAP Kinase Signaling System
• Male
• Myocardial Infarction (metabolism)
• Myocytes, Cardiac (metabolism)
• Rats
• Rats, Sprague-Dawley
• Syndecan-1 (blood, genetics, metabolism)
• Ventricular Remodeling (genetics)
• p38 Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism)