title: Ascorbic Acid Protects against Hypertension through Downregulation of ACE1 Gene Expression Mediated by Histone Deacetylation in Prenatal Inflammation-Induced Offspring.
abstract: Hypertension is a major risk factor for cardiovascular and cerebrovascular disease. Prenatal exposure to lipopolysaccharide (LPS) leads to hypertension in a rat offspring. However, the mechanism is still unclear. This study unraveled epigenetic mechanism for this and explored the protective effects of ascorbic acid against hypertension on prenatal inflammation-induced offspring. Prenatal LPS exposure resulted in an increase of intrarenal oxidative stress and enhanced angiotensin-converting enzyme 1 (ACE1) gene expression at the mRNA and protein levels in 6- and 12-week-old offspring, correlating with the augmentation of histone H3 acetylation (H3AC) on the ACE1 promoter. However, the prenatal ascorbic acid treatment decreased the LPS-induced expression of ACE1, protected against intrarenal oxidative stress, and reversed the altered histone modification on the ACE1 promoter, showing the protective effect in offspring of prenatal LPS stimulation. Our study demonstrates that ascorbic acid is able to prevent hypertension in offspring from prenatal inflammation exposure. Thus, ascorbic acid can be a new approach towards the prevention of fetal programming hypertension.
authors.affiliation: Department of Obstetrics and Gynecology, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Na
authors.initials: N
authors.lastname: Yin
authors.affiliation: Institute of Materia Medica, College of Pharmacy, Third Military Medical University, Chongqing, China.
authors.forename: Youcai
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Gastroenterology, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Obstetrics and Gynecology, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Yinhu
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Obstetrics and Gynecology, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Pu
authors.affiliation: Department of Obstetrics and Gynecology, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Yingru
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Obstetrics and Gynecology, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Obstetrics and Gynecology, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.|The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, US.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yu
authors.affiliation: Institute of Materia Medica, College of Pharmacy, Third Military Medical University, Chongqing, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Yi
mesh_terms: D000107:Acetylation; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001205:Ascorbic Acid / Q000494:pharmacology*; D001794:Blood Pressure; D001835:Body Weight; D018899:CpG Islands; D044127:Epigenesis, Genetic; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006657:Histones / Q000378:metabolism*; D006973:Hypertension / Q000378:metabolism / Q000517:prevention & control*; D007249:Inflammation / Q000378:metabolism; D007668:Kidney / Q000473:pathology; D008070:Lipopolysaccharides / Q000378:metabolism; D018384:Oxidative Stress; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012307:Risk Factors
chemical_list: D000975:Antioxidants; D006657:Histones; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D007703:Peptidyl-Dipeptidase A; D001205:Ascorbic Acid