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Myocardial fibrosis (MF) is the common pathology of many cardiovascular diseases at the end stage, however, the underling mechanism remains unclear. Given Prenatal exposure to Lipopolysaccharide (LPS) produces hypertension in adult offspring rats, the present study was to explore the effects of prenatal inflammation on MF in the offspring rats and to further assess its susceptibility to cardiovascular diseases.
Pregnant rats were treated intraperitoneally on gestation Days 8, 10 and 12 with saline, LPS (0.79 mg/kg), respectively. Histopathological alteration, fibrosis evaluation and α-SMA immunofluorescent patterns in the left ventricle (LV) were analyzed in offspring at the age of 8 weeks. The primary cardiac fibroblasts was stimulated with LPS (10 μg/ml), AngII (20 μM), CBX (400 μM), LPS (10 μg/ml) + AngII (20 μM), LPS (10 μg/ml) + CBX (400 μM) and AngII (20 μM) + CBX (400 μM), respectively. Cx43, LC3, DNMT 1, DNMT 3A and DNMT 3B in LV and the fibroblasts, whose mRNA and protein expression were performed as well.
Prenatal LPS exposure leads to obvious collagen deposition and morphological abnormalities in the LV. Furthermore, the CVF index and α-SMA immunofluorescence expression were both increased. Prenatal LPS exposure also decreased the protein and mRNA expression of Cx43, LC3 and DNMT 1in the LV from offspring rats. The protein and mRNA expression of Cx43 and LC3 was decreased in fibroblast treated with LPS and AngII, DNMT 1, however, was increased. Cx43 inhibitor CBX, which decreased the protein and mRNA expression of Cx43, LC3 and DNMT1 induced by LPS and AngII, respectively. In addition, there weren’t synergistic effects of LPS and AngII on protein and mRNA expression of Cx43, LC3 and DNMT1.
Abnormal expression of Cx43 may be related to autophagy and DNA methylation, which was responsible for MF in offspring rats induced by maternal LPS exposure during pregnancy.