{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:11:33Z","timestamp":1791922293028,"version":"4.3.4"},"reference-count":30,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T00:00:00Z","timestamp":1672704000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Perinatal malnutrition affects vascular functions, and calcium is important in vascular regulations. It is unknown whether and how perinatal maternal high-fat diets (MHF)-mediated vascular dysfunction occurs via the angiotensin-PKC-L-type-calcium-channels (LTCC) axis. This study determined angiotensin II (AII) roles in the PKC-LTCC axis in controlling calcium influx in the arteries of offspring after perinatal MHF. Mesenteric arteries (MA) and smooth muscle cells (SMCs) from 5-month-old offspring rats were studied using physiological, ion channel, molecular, and epigenetic analysis. Pressor responses to AII were significantly increased in the free-moving MHF offspring rats. In cell experiments, MA-SMC proliferation was enhanced, and associated with thicker vascular wall in the obese offspring. Imaging analysis showed increase of fluorescence Ca2+ intensity in the SMCs of the MHF group. Angiotensin II receptor (AT1R)-mediated PKC-LTCC axis in vasoconstrictions was altered by perinatal MHF via reduced DNA methylation at specific CpG sites of Agtr1a and Prkcb gene promoters at the transcription level. Accordingly, mRNA and protein expression of AT1R and PKC\u03b2 in the offspring MA were increased, contributing to enhanced Ca2+ currents and vascular tone. The results showed that DNA methylation resulted in perinatal MHF-induced vascular disorders via altered AT1-PKC-LTCC pathway in resistance arteries of the offspring, providing new insights into the pathogenesis and early prevention\/treatments for hypertension in developmental origins.<\/jats:p>","DOI":"10.3390\/nu15010245","type":"journal-article","created":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T02:15:42Z","timestamp":1672798542000},"page":"245","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Perinatal Fat-Diets Increased Angiotensin II-Mediated Ca2+ through PKC-L-Type Calcium Channel Axis in Resistance Arteries via Agtr1a-Prkcb Gene Methylation"],"prefix":"10.3390","volume":"15","author":[{"given":"Qiutong","family":"Zheng","sequence":"first","affiliation":[{"name":"Institute for Fetology, First Hospital of Soochow University, Suzhou 215006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"He","sequence":"additional","affiliation":[{"name":"Institute for Fetology, First Hospital of Soochow University, Suzhou 215006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingjun","family":"Li","sequence":"additional","affiliation":[{"name":"Institute for Fetology, First Hospital of Soochow University, Suzhou 215006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"Rui","sequence":"additional","affiliation":[{"name":"Nanjing Maternity and Child Health Care Hospital, Nanjing Medical University, Nanjing 210004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Li","sequence":"additional","affiliation":[{"name":"Maternal and Child Health Care Hospital of Wuxi, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute for Fetology, First Hospital of Soochow University, Suzhou 215006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Ye","sequence":"additional","affiliation":[{"name":"Maternal and Child Health Care Hospital of Wuxi, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ze","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute for Fetology, First Hospital of Soochow University, Suzhou 215006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojun","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute for Fetology, First Hospital of Soochow University, Suzhou 215006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Tang","sequence":"additional","affiliation":[{"name":"Institute for Fetology, First Hospital of Soochow University, Suzhou 215006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6319-0206","authenticated-orcid":false,"given":"Zhice","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute for Fetology, First Hospital of Soochow University, Suzhou 215006, China"},{"name":"Maternal and Child Health Care Hospital of Wuxi, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Barnes, M.D., Heaton, T.L., Goates, M.C., and Packer, J.M. 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