The Role of Akap5 Histone Acetylation in Improving Vascular Function in Hypertensive Offspring Induced by Exercise during Pregnancy

Objective: To investigate the role of histone acetylation of AKAP150 gene(Akap5) in improving vascular function in hypertensive offspring induced by maternal exercise during pregnancy. Methods: Pregnant Wistar-Kyoto rats(WKYs) and spontaneously hypertensive rats(SHRs) were randomly assigned to either sedentary(p-WKY-SED and p-SHR-SED) or exercise group(p-WKY-EX and p-SHR-EX), and the rats of exercise groups conducted swimming training from gestation day 1(GD1) to GD20. The mesenteric arteries(MAs) were collected at embryonic day 21(ED21) and 3 months(3M) from male offsprings. The isolated microvessels, patch clamp, Western blot, qPCR, and ChIP-qPCR were utilized to assess vascular CaV1.2 channel function,AKAP150 protein and mRNA expression, and histone H3 lysine 9 acetylation(H3K9ac) levels in the Akap5 gene promoter. Results:Prenatal exercise significantly decreased the blood pressure and inhibited the upregulation of CaV1.2 channel function in 3M male offspring from p-SHR-EX(P<0.05). In both ED21 and 3M rat MAs, maternal exercise decreased the AKAP150 mRNA and protein expression, as well as H3K9ac levels in the Akap5 gene promoter region among p-SHR-EX male offspring(P<0.05). Conclusions:Maternal exercise during pregnancy can decrease H3K9ac levels in the Akap5 gene promoter region within fetal rat MAs myocytes,and subsequently inhibit AKAP150 gene transcription and protein expression, ultimately attenuating the upregulation of vascular CaV1.2 channel function in adult rats with hypertensive backgrounds, which result in a reduction in blood pressure.