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.

Prenatal inflammation exposure-programmed cardiovascular diseases and potential prevention

“…There are some limited exploratory studies seeking potential effective preventive strategies during pregnancy or in young offspring by using PIE animal models. We found that pharmacological treatments in the second trimester with PDTC could effectively prevent PIE-programmed hypertension, vascular damage Hao, Zhang, Yuan, et al, 2010), and myocardial remodeling (Chen, et al, 2015;Y. Wei, et al, 2013) in rats.…”

“…Zhao, Zhang, Cao, Liu, & Li, 2014). In addition, animals that were maternally exposed to LPS or zymosan had increased levels of myocardial fibrosis and myocardial remodeling (Chen, et al, 2015;Y. Wei, et al, 2013), significantly reduced glomerular numbers and creatinine clearance rates, but higher urinary protein levels, indicating renal injury (Hao, Zhang, Yuan, et al, 2010) (Fig.…”

“…Zhao, et al, 2014), which is likely due to a persistently lower level of IκBα , a critical molecule for retaining NF-κB dimers in the cytoplasm in an inactive state (Ruland, 2011). Both prenatal or postnatal NF-κB inhibition by pyrrolidine dithiocarbamate (PDTC) was able to prevent hypertension and alleviate damage to the myocardium (Chen, et al, 2015), vasculature system and kidney (Guo, et al, 2016).…”

Sex differences in major depression and comorbidity of cardiometabolic disorders: impact of prenatal stress and immune exposures

“…This is interesting as prenatal IL-6 exposure has also been implicated in neurodevelopment and behavioral abnormalities associated with schizophrenia [150]. In addition, injecting the endotoxin LPS to pregnant dams produced diastolic dysfunction [196], associated with cardiac pathological remodeling in the heart involving hypertrophy, fibrosis [197], and apoptosis [196] in the adult offspring. The functional consequence of a prenatal inflammatory environment was impaired diastolic [196] and aortic dysfunction characterized by altered reactivity and connexin expression [198].…”

The peptide compound urantide regulates collagen metabolism in atherosclerotic rat hearts and inhibits the JAK2/STAT3 pathway

“…atherosclerosis (aS) is a serious disease that causes hypoxic ischemia of the heart and leads to disordered collagen metabolism during its progression (1,2). Multiple studies have revealed that the urotensin ii/urotensin report (uii/uT) system, which is composed of uii and its receptor, G protein-coupled receptor 14 (GPr14), serves an important role in various diseases, including aS and heart disease (3,4).…”