{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T01:11:53Z","timestamp":1773018713208,"version":"3.50.1"},"reference-count":65,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,2,22]],"date-time":"2026-02-22T00:00:00Z","timestamp":1771718400000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Nutrition Food Res"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Excessive fat intake is a well\u2010established risk for hypertension; perinatal nutritional imbalances could increase vascular risks, but underlying mechanisms remain unclear. Endothelin\u20101 (ET\u20101), a potent vasoconstrictor, is implicated in cardiovascular diseases. This study aimed to address this gap by investigating ET\u20101 receptor\u2010mediated pathways with high\u2010fat\u2010diet (HFD) during pregnancy and lactation. Vascular function, Ca\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    signaling, molecular expression, and DNA methylation were assessed in mesenteric arteries (MA) of offspring. HFD offspring exhibited increased fetal\/adult weight, thickened MA wall, and enhanced ET\u20101\u2010mediated vasoconstriction. Mechanistically, perinatal HFD upregulated ET\u20101 receptors (ETAR\/ETBR) via hypomethylation of their gene promoters (Ednra\/Ednrb), which augmented ET\u20101\u2010induced Ca\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    currents, fluorescence Ca\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    transients, and vascular tone. Which relied on the PKC\u2010LTCC axis (strengthened by PKC activator and LTCC agonist) and altered intracellular Ca\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    handling (via ryanodine receptors and sarcoplasmic\/endoplasmic reticulum Ca\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    \u2010ATPase), but were independent of IP3 receptors. ETAR\/ETBR blockers attenuated the hypercontractility, confirming receptor\u2010mediated effects. This is the first study to reveal that perinatal HFD persistently enhances vascular re\u2010activity via DNA hypomethylation of ET receptors and PKC\u2010LTCC axis. These findings not only reveal a mechanism linking perinatal HFD to adult vascular hypercontractility but also highlight ET receptors and DNA methylation as potential targets for early intervention of developmental origins of cardiovascular disease.\n                  <\/jats:p>","DOI":"10.1002\/mnfr.70415","type":"journal-article","created":{"date-parts":[[2026,2,22]],"date-time":"2026-02-22T14:10:52Z","timestamp":1771769452000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Perinatal High\u2010Fat Diet Induces Vascular Hypercontractility via DNA Hypomethylation of Endothelin Receptors and PKC\u2010LTCC Axis Activation in Male Offspring"],"prefix":"10.1002","volume":"70","author":[{"given":"Qiutong","family":"Zheng","sequence":"first","affiliation":[{"name":"Wuxi Maternity and Child Health Care Hospital Affiliated Women's Hospital of Jiangnan University &amp; Obstetrics and Gynecology Hospital Institute of 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