Yun He, Ze Zhang, Qiutong Zheng, Hongyu Su, Mingxing Liu, Xueyi Chen, Linglu Qi, Yumeng Zhang, Zhice Xu, Jiaqi Tang
{"title":"Paternal alcohol exposure affected offspring mesenteric artery via ROS-Cacna1c and DNA hypomethylation.","authors":"Yun He, Ze Zhang, Qiutong Zheng, Hongyu Su, Mingxing Liu, Xueyi Chen, Linglu Qi, Yumeng Zhang, Zhice Xu, Jiaqi Tang","doi":"10.1097/HJH.0000000000003947","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Paternal preconception alcohol exposure affects fetal development; however, it is largely unknown about the influences on offspring vasculature and mechanisms.</p><p><strong>Methods: </strong>Offspring born form paternal rats treated with alcohol or water before pregnant was raised until 3 months of age. Vessel tone of mesenteric arteries was detected using myograph system; whole-cell calcium channel current in smooth muscle cells was tested using patch-clamp; molecule expressions were detected with real-time PCR, western blotting, and Dihydroethidium (DHE); DNA methylations were determined using targeted bisulfate sequencing assay. Following 5-aza-2'-deoxycytidine incubation, vessel tone in offspring mesenteric artery and Cacna1c expression in A7r5 was tested.</p><p><strong>Results: </strong>When comparing with the control, stress-strain curve was left-shifted in alcohol. There was lower incremental distensibility and endothelium-dependent dilation associated with endothelial nitric oxide synthase. Agonists-induced constrictions were greater in alcohol offspring than that in control, associated with higher expression of AT1R, Cacna1c, and reactive oxygen species (ROS). Baseline and Ang II-stimulated calcium channel currents were higher in alcohol group. Tempol and apocynin could restore Ang II-increased constriction and calcium channel current in alcohol offspring. When comparing with the control, there was lower DNA methylation of Cacna1c promotor in alcohol offspring mesenteric artery and in paternal sperm. 5-aza-2'-deoxycytidine increased contraction in control offspring mesenteric artery and Cacna1c expression in A7r5.</p><p><strong>Conclusion: </strong>Paternal preconception alcohol exposure-affected offspring mesenteric artery was via ROS-Cacna1c. Abnormal offspring vascular functions might be inherited via DNA hypomethylation of Cacna1c promotor from paternal sperm exposed to alcohol. These data gained provided important clues for cardiovascular disorders at germ cell origin.</p>","PeriodicalId":16043,"journal":{"name":"Journal of Hypertension","volume":" ","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Hypertension","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/HJH.0000000000003947","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PERIPHERAL VASCULAR DISEASE","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Paternal preconception alcohol exposure affects fetal development; however, it is largely unknown about the influences on offspring vasculature and mechanisms.
Methods: Offspring born form paternal rats treated with alcohol or water before pregnant was raised until 3 months of age. Vessel tone of mesenteric arteries was detected using myograph system; whole-cell calcium channel current in smooth muscle cells was tested using patch-clamp; molecule expressions were detected with real-time PCR, western blotting, and Dihydroethidium (DHE); DNA methylations were determined using targeted bisulfate sequencing assay. Following 5-aza-2'-deoxycytidine incubation, vessel tone in offspring mesenteric artery and Cacna1c expression in A7r5 was tested.
Results: When comparing with the control, stress-strain curve was left-shifted in alcohol. There was lower incremental distensibility and endothelium-dependent dilation associated with endothelial nitric oxide synthase. Agonists-induced constrictions were greater in alcohol offspring than that in control, associated with higher expression of AT1R, Cacna1c, and reactive oxygen species (ROS). Baseline and Ang II-stimulated calcium channel currents were higher in alcohol group. Tempol and apocynin could restore Ang II-increased constriction and calcium channel current in alcohol offspring. When comparing with the control, there was lower DNA methylation of Cacna1c promotor in alcohol offspring mesenteric artery and in paternal sperm. 5-aza-2'-deoxycytidine increased contraction in control offspring mesenteric artery and Cacna1c expression in A7r5.
Conclusion: Paternal preconception alcohol exposure-affected offspring mesenteric artery was via ROS-Cacna1c. Abnormal offspring vascular functions might be inherited via DNA hypomethylation of Cacna1c promotor from paternal sperm exposed to alcohol. These data gained provided important clues for cardiovascular disorders at germ cell origin.
期刊介绍：
The Journal of Hypertension publishes papers reporting original clinical and experimental research which are of a high standard and which contribute to the advancement of knowledge in the field of hypertension. The Journal publishes full papers, reviews or editorials (normally by invitation), and correspondence.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
