title: 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.
authors.affiliation: Institute of Materia Medical, College of Pharmacy, Third Military Medical University, Chongqing 400038, China. kaoyanchenxin@163.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, Xiangyang Central Hospital, Xiangyang 441021, China. tyjylx@163.com.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Institute of Materia Medical, College of Pharmacy, Third Military Medical University, Chongqing 400038, China. gm0716@126.com.
authors.forename: Meng
authors.initials: M
authors.lastname: Gao
authors.affiliation: Institute of Materia Medical, College of Pharmacy, Third Military Medical University, Chongqing 400038, China. qsg18323213193@163.com.
authors.forename: Shugang
authors.initials: S
authors.lastname: Qin
authors.affiliation: Institute of Materia Medical, College of Pharmacy, Third Military Medical University, Chongqing 400038, China. jazi891@aliyun.com.
authors.forename: Jianzhi
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Institute of Materia Medical, College of Pharmacy, Third Military Medical University, Chongqing 400038, China. lpsh008@aliyun.com.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D005260:Female; D005355:Fibrosis; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D008070:Lipopolysaccharides / Q000276:immunology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D009206:Myocardium / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D011759:Pyrrolidines / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013859:Thiocarbamates / Q000627:therapeutic use; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; D016212:Transforming Growth Factor beta; D019716:Tissue Inhibitor of Metalloproteinase-2; C020972:pyrrolidine dithiocarbamic acid; D020778:Matrix Metalloproteinase 2
keywords: lipopolysaccharide; myocardial fibrosis; pregnant; pyrrolidine dithiocarbamic acid