Effects of PPAR-y in the Myocardium on the Development of Ventricular Septation

Ventricular septum defects(VSDs)are common types of congenital heart diseases caused by developmental defect;they contribute to 25%-30%of all adult congenital heart diseases.The peroxisome proliferator-activated receptor gamma(PPAR-y)is widely expressed in mammalian tissues and in the immune system,regulating cell differentiation and immune and inflammatory responses.The PPAR-y gene has recently been found crucial for heart development,but the mechanism of action is not clear.This study aims to investigate the effects of the PPAR-y gene in the myocardium on the development of ventricular septation.In this study,we applied Cre-loxP recombination enzyme(CRE)technology to downregulate the expression of the PPAR-y gene in different cardiac tissues,RT-PCR to examine the expression of the c-fos and TGF-B!genes,and histology staining to check the defect of embryonic heart at embryonic day 14.5(E14.5).We found that the downregulation of the PPAR-p gene resulted in a ventricular membranous septation defect of the embryonic heart at E14.5.Furthermore,only conversion of a Tnt:Cre,but not Mef2c:Cre,Tie2:Cre,or Wnt:Cre PPAR-T floxed allele to a null allele resulted in VSD.PPAR-/mi-Orv+embryos showed increascs in atrioventricular(AV)-cushion cells and the expression of c-fos gene but no change in the expression of TGF-B1 at E10.5.Our study demonstrates PPAR-N in the myocardium is required for ventricular septation through regulation of AV-cushion cell proliferation by a Tntc-fos signal.