{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T20:48:10Z","timestamp":1790196490512,"version":"4.1.0"},"reference-count":46,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T00:00:00Z","timestamp":1744848000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R56HL151602-01A1"],"award-info":[{"award-number":["1R56HL151602-01A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01TW164306-02A1"],"award-info":[{"award-number":["1R01TW164306-02A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R21NS139920-01A1"],"award-info":[{"award-number":["1R21NS139920-01A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Early-onset heart failure is a major treat to healthy aging individuals with HIV-1 infection. Women with HIV-1 infection (WLWH) are especially vulnerable and develop heart failure with preserved ejection fraction (HFpEF), of which left ventricular diastolic dysfunction, vascular deficits, myocardial infarction, and fibrosis are major components. HIV-infected rodent models that exhibit these pathophysiological features remain under-reported, and this has left a void in our understanding of their molecular causes and therapeutic strategies to blunt its development. Here, we show that female NOD.Cg-PrkdcscidIl2rgtm1Wjl\/SzJ humanized mice (Hu-mice) infected with HIV-1ADA and treated for 13 weeks with dolutegravir (DTG)\/tenofovir disoproxil fumarate (TDF)\/emtricitabine (FTC) develop progressive diastolic dysfunction with preserved ejection fraction (E:A ratio, E:e\u2032, IVRT, left atrial volume and global longitudinal strain increased by 32.1 \u00b1 5.1%, 28.2 \u00b1 5.6%, 100.2 \u00b1 12.6%, 26.6 \u00b1 4.2% and 32.5 \u00b1 4.3%, respectively). In vivo photoacoustic imaging revealed a 30.4 \u00b1 6.8% reduction in saturated oxygenated hemoglobin in the anterior wall of the heart. The ex vivo analysis of hearts showed a reduction in density of perfused microvessels\/ischemia (30.6 \u00b1 6.2%) with fibrosis (20.2 \u00b1 1.2%). The HIF-1\u03b1 level was increased 2.6 \u00b1 0.5-fold, while inflammation-induced serum semicarbazide amine oxidase and glycolysis byproduct methylglyoxal increased 2-fold and 2.1-fold, respectively. Treating H9C2 cardiac myocytes with DTG, FTC and TDF dose-dependently increased expression of HIF-1\u03b1. These data show that HIV-infected Hu-mice treated with DTG\/TDF\/FTC for thirteen weeks develop cardiac diastolic dysfunction, with vascular deficits, ischemia, and fibrosis like those reported in women living with HIV-1 infection (WLWH). They also show that DTG, TDF, and FTC treatment can increase total HIF-1\u03b1 in H9C2 cells.<\/jats:p>","DOI":"10.3390\/ijms26083801","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T06:53:46Z","timestamp":1744872826000},"page":"3801","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Diastolic Dysfunction with Vascular Deficits in HIV-1-Infected Female Humanized Mice Treated with Antiretroviral Drugs"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0788-6919","authenticated-orcid":false,"given":"Fadhel A.","family":"Alomar","sequence":"first","affiliation":[{"name":"Department of Pharmacology, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prasanta K.","family":"Dash","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology and Experimental Neuroscience, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5800, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahendran","family":"Ramasamy","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology and Experimental Neuroscience, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5800, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8073-5094","authenticated-orcid":false,"given":"Zachary L.","family":"Venn","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology and Experimental Neuroscience, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5800, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean R.","family":"Bidasee","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology and Experimental Neuroscience, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5800, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0785-1292","authenticated-orcid":false,"given":"Chen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology and Experimental Neuroscience, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5800, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan T.","family":"Hackfort","sequence":"additional","affiliation":[{"name":"Cellular and Integrative Physiology, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santhi","family":"Gorantla","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology and Experimental Neuroscience, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5800, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4165-8362","authenticated-orcid":false,"given":"Keshore R.","family":"Bidasee","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia"},{"name":"Environmental, Agricultural and Occupational Health, University of Nebraska Medical Center, Omaha, NE 68198-5800, USA"},{"name":"Nebraska Redox Biology Center, Lincoln, NE 68503, USA"},{"name":"Center for Heart and Vascular Research, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1071\/SH11046","article-title":"Life expectancy of HIV-positive adults: A review","volume":"8","author":"May","year":"2011","journal-title":"Sex. 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