{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:06:27Z","timestamp":1791234387327,"version":"4.1.0"},"reference-count":52,"publisher":"American Society for Clinical Investigation","issue":"13","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":153,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017540","name":"NHLBI Division of Intramural Research","doi-asserted-by":"crossref","award":["HL167656,HL148123"],"award-info":[{"award-number":["HL167656,HL148123"]}],"id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,8]]},"abstract":"<jats:p>Cardiovascular disease (CVD) contributes to morbidity and mortality in people with HIV (PWH) receiving antiretroviral therapy (ART). In the REPRIEVE trial, pitavastatin reduced atherosclerotic CVD risk to a magnitude inconsistent with pitavastatin\u2019s impact solely on LDL cholesterol and inflammation. Here, atorvastatin and ART used in REPRIEVE, including tenofovir, emtricitabine, and dolutegravir, ritonavir and darunavir were examined in 2 mouse models: transgenic HIV-Tg26 mice and HIV-PDX mice engrafted with T cells from PWH. HIV-Tg26 and HIV-PDX mice had higher cardiac fibrosis than littermate controls without HIV. Administration of tenofovir, emtricitabine, and dolutegravir or ritonavir, but not darunavir, resulted in an approximately 2-fold increase in fibrosis. Mice depleted of platelet TGF-\u03b21 or treated with atorvastatin were partially protected from HIV- and ART-induced cardiac fibrosis, steatosis, and diastolic dysfunction. Atorvastatin\u2019s effects were independent of changes in inflammatory cytokines, which correlated with reduced platelet activation and TGF-\u03b2 signaling in cardiac endothelial cells, fibroblasts, and macrophages undergoing mesenchymal transition. Our results indicate that certain ART regimens accelerate HIV-associated CVD characterized by heart failure with preserved ejection fraction via platelet TGF-\u03b21\u2013dependent processes, which were mitigated by atorvastatin. Our findings provide a potential mechanism for the pleiotropic effects of statins in HIV\/ART-linked CVD, which could be targeted by antiplatelet agents or inhibition of TGF-\u03b2 signaling.<\/jats:p>","DOI":"10.1172\/jci.insight.198647","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T15:27:17Z","timestamp":1771255637000},"source":"Crossref","is-referenced-by-count":3,"title":["Atorvastatin suppresses HIV\/antiretroviral drug\u2013induced cardiac fibrosis and dysfunction in mice by blocking platelet TGF-\u03b21 signaling"],"prefix":"10.1172","volume":"11","author":[{"given":"Kumar","family":"Subramani","sequence":"first","affiliation":[{"name":"Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denys","family":"Babii","sequence":"additional","affiliation":[{"name":"Cardiovascular Biology Research Program, Oklahoma Medical 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