title: Maternal High-Fat Diet Causes a Sex-Dependent Increase in AGTR2 Expression and Cardiac Dysfunction in Adult Male Rat Offspring.
abstract: Maternal high-fat diet (HFD) is associated with cardiovascular disease later in life. This study tested the hypothesis that maternal HFD causes programming of increased cardiac angiotensin II receptor type 2 (AGTR2) expression, resulting in heightened cardiac susceptibility to ischemic injury in male offspring in a sex-dependent manner. Pregnant rats were divided between control and HFD (HFD-fed during gestation) groups. Maternal HFD resulted in cardiac hypertrophy in only male offspring, but had no effect on cardiac systolic and diastolic function in both male and female offspring. In addition, maternal HFD increased heart susceptibility to ischemia-reperfusion injury in adult male offspring, but not female offspring. There was an increase in Agtr2 mRNA and protein abundance in male, but not female offspring. However, maternal HFD had no effect on angiotensin II receptor type 1 (AGTR1) expression in both male and female offspring. HFD resulted in decreased glucocorticoid receptors (GRs) binding to the glucocorticoid response elements at the Agtr2 promoter, which was due to decreased GRs in the hearts of adult male offspring. Inhibition of AGTR2 with PD123319 abrogated maternal HFD-induced increase in cardiac ischemic vulnerability in male adult rats. The results demonstrate that maternal HFD causes programming of increased Agtr2 gene expression in the heart by downregulation of GR, contributing to the heightened cardiac vulnerability to ischemic injury in adult male offspring in a sex-dependent manner.
authors.affiliation: Department of Pharmacology, Guangzhou Medical University, Guangzhou, PR China xueqin1980@hotmail.com.
authors.forename: Qin
authors.initials: Q
authors.lastname: Xue
authors.affiliation: Department of Pharmacology, Guangzhou Medical University, Guangzhou, PR China.
authors.forename: Pinxian
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Guangzhou Medical University, Guangzhou, PR China.
authors.forename: Xiongxiong
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Guangzhou Medical University, Guangzhou, PR China.
authors.forename: Guiping
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Center for Perinatal Biology, Department of Physiology and Pharmacology, Loma Linda University School of Medicine, Loma Linda, California.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Patterson
authors.affiliation: Department of Pharmacology, Guangzhou Medical University, Guangzhou, PR China jiandongluo@hotmail.com.
authors.forename: Jiandong
authors.initials: J
authors.lastname: Luo
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced / Q000235:genetics; D059305:Diet, High-Fat / Q000009:adverse effects*; D005260:Female; D047109:Fetal Development; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006331:Heart Diseases / Q000139:chemically induced* / Q000235:genetics; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D009203:Myocardial Infarction / Q000235:genetics / Q000473:pathology; D017202:Myocardial Ischemia / Q000235:genetics; D015428:Myocardial Reperfusion Injury / Q000235:genetics; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044139:Receptor, Angiotensin, Type 2 / Q000096:biosynthesis* / Q000235:genetics; D012727:Sex Characteristics
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D007093:Imidazoles; D011725:Pyridines; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; C073402:PD 123319
keywords: angiotensin II receptors; fetal programming; glucocorticoid receptor; heart; maternal high-fat diet