Prenatal exposure to lipopolysaccharide results in myocardial fibrosis in rat offspring

Abstract

The epigenetic plasticity hypothesis indicates that exposure during pregnancy may cause adult-onset disorders, including hypertension, myocardial infarction and heart failure. Moreover, myocardial fibrosis coincides with hypertension, myocardial infarction and heart failure. This study was designed to investigate the effects of prenatal exposure to lipopolysaccharide (LPS) on myocardial fibrosis. The result showed that at six and 16 weeks of age, the LPS-treated offspring exhibited increased collagen synthesis, an elevated cardiac index (CI), higher mRNA levels of TIMP-2 and TGFβ and a reduced mRNA level of MMP2. The protein levels corresponded to the mRNA levels. The offspring that were prenatally treated with pyrrolidine dithiocarbamic acid (PDTC), an inhibitor of NF-κB, displayed improvements in the CI and in collagen synthesis. Moreover, PDTC ameliorated the expression of cytokines and proteins associated with myocardial fibrosis. The results showed that maternal inflammation can induce myocardial fibrosis in offspring during aging accompanied by an imbalance of TIMP-2/MMP2 and TGFβ expression.