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Further, PGI2 signaling exhibits immunomodulatory properties that largely promote an anti-inflammatory state. Inflammation and immune activity are associated with the development of hypertension. However, it remains unknown whether exogeneous PGI2 can restrain the immune and inflammatory responses in the context of hypertension. A phenome-wide association study evaluated single-nucleotide polymorphisms (SNPs) in the receptor for PGI2, IP (gene name PTGIR), and the associated odds of developing cardiovascular pathologies. C57Bl\/6J mice underwent one of two models to evaluate the effect of an exogenous PGI2 analog on aortic inflammation and hypertension. Mice were either administered the PGI2 analog, treprostinil (TPL), at the initiation of angiotensin II (Ang II) infusion to determine the effect of TPL on the development of inflammation and hypertension, or mice were administered TPL after 2\u00a0weeks of Ang II to determine the ability of TPL to reduce blood pressure and inflammation in established hypertension. Humans who were heterozygous for an SNP in IP had a significantly greater odds ratio for several vascular pathologies compared to controls. Mice that received TPL at the onset of Ang II infusion were protected from developing hypertension and exhibited reduced aortic inflammation. Mice that received TPL two weeks after initiation of Ang II infusion exhibited a significant reduction in their blood pressure, decreased aortic inflammation, diminished aortic fibrosis, and fewer splenic Th1 cells compared to vehicle treatment. Exogeneous PGI2 signaling protects against the development and\/or maintenance of Ang II-induced hypertension, possibly through inhibition of Th1 cell function.<\/jats:p>","DOI":"10.1042\/cs20250501","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T11:04:37Z","timestamp":1780571077000},"page":"1303-1316","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Treprostinil reduces blood pressure and aortic inflammation in hypertension"],"prefix":"10.1042","volume":"140","author":[{"given":"Raghad","family":"AlMotairy","sequence":"first","affiliation":[{"name":"1Department of Cell Biology, Anatomy, and Physiology, Indiana University School of Medicine, Indianapolis, IN, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md\u00a0Mahbub","family":"Ullah","sequence":"additional","affiliation":[{"name":"1Department of Cell Biology, Anatomy, and Physiology, Indiana 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