Sdc1 Overexpression Inhibits the p38 MAPK Pathway and Lessens Fibrotic Ventricular Remodeling in MI Rats
- PDF / 662,447 Bytes
- 13 Pages / 595.276 x 790.866 pts Page_size
- 72 Downloads / 178 Views
Sdc1 Overexpression Inhibits the p38 MAPK Pathway and Lessens Fibrotic Ventricular Remodeling in MI Rats Juan Lei,1 Shengneng Xue,2 Wei Wu,1,3 Shuxian Zhou,1 Yuling Zhang,1 Guiyi Yuan,1 and Jingfeng Wang1
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 (n048) 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. KEY WORDS: syndecan-1; myocardial infarction; ventricular remodeling; P38 MAPK.
and arrhythmia may result. This pathological remodeling of myocardial tissue outside the infarction area is thought to be due to an excessive inflammatory response to the injury caused by the infarction. A clear understanding of the mechanisms responsible for this excessive inflammatory response and subsequent pathological remodeling would give us insight into what therapeutic measures would alleviate it. The cell-associated heparan glycoprotein, syndecan-1 (Sdc1) is involved, among other things, in tissue repair. However, contradictions about its actions have been reported in that Sdc1 knockout and Sdc1 overexpression have both been reported to be detrimental to the tissue repair response [1]. Previously, we have shown that expression of Sdc1 is upregulated in rats with MI and that soluble serum Sdc1 levels are a potential biomarker for this condition [2]. The question
INTRODUCTION One of the possible consequences during recovery from myocardial infarction (MI) is fibrotic remodeling of the ventricles. During this
Data Loading...
