{"doi":"10.3390/ijms26083801","title":"Diastolic Dysfunction with Vascular Deficits in HIV-1-Infected Female Humanized Mice Treated with Antiretroviral Drugs","abstract":"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′, IVRT, left atrial volume and global longitudinal strain increased by 32.1 ± 5.1%, 28.2 ± 5.6%, 100.2 ± 12.6%, 26.6 ± 4.2% and 32.5 ± 4.3%, respectively). In vivo photoacoustic imaging revealed a 30.4 ± 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 ± 6.2%) with fibrosis (20.2 ± 1.2%). The HIF-1α level was increased 2.6 ± 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-1α. 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-1α in H9C2 cells.","journal":"International Journal of Molecular Sciences","year":2025,"id":540930,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9523,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":388569,"name":"Prasanta K. Dash","orcid":"0000-0002-8250-2359","position":1,"is_corresponding":false},{"id":1428888,"name":"Ramasamy Mahendran","orcid":"0000-0001-5037-8640","position":2,"is_corresponding":false},{"id":964826,"name":"Zachary L. Venn","orcid":"0000-0002-5634-959X","position":3,"is_corresponding":false},{"id":965306,"name":"Sean R. Bidasee","orcid":null,"position":4,"is_corresponding":false},{"id":490272,"name":"Chen Zhang","orcid":"0000-0002-0785-1292","position":5,"is_corresponding":false},{"id":284730,"name":"Bryan T. Hackfort","orcid":"0000-0002-8472-3622","position":6,"is_corresponding":false},{"id":236489,"name":"Santhi Gorantla","orcid":"0000-0002-9064-1084","position":7,"is_corresponding":false},{"id":388572,"name":"Keshore R. Bidasee","orcid":"0000-0003-4165-8362","position":8,"is_corresponding":false},{"id":388570,"name":"Fadhel A. Alomar","orcid":"0000-0003-0788-6919","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-19T02:52:42.901627Z","pmid":"40332423","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}