Rodriguez-Irizarry, Valerie J.Schneider, Alina C.Ahle, DanielSmith, Justin M.Suarez-Martinez, Edu B.Salazar, Ethan A.McDaniel Mims, BrianyellRasha, FahmidaMoussa, HannaMoustaïd-Moussa, NaimaPruitt, KevinFonseca, MarceloHenriquez, MauricioClauss, Matthias A.Grisham, Matthew B.Almodovar, Sharilyn2024-05-302024-05-302022-08-05Rodriguez-Irizarry VJ, Schneider AC, Ahle D, et al. Mice with humanized immune system as novel models to study HIV-associated pulmonary hypertension. Front Immunol. 2022;13:936164. Published 2022 Aug 5. doi:10.3389/fimmu.2022.936164https://hdl.handle.net/1805/41103People living with HIV and who receive antiretroviral therapy have a significantly improved lifespan, compared to the early days without therapy. Unfortunately, persisting viral replication in the lungs sustains chronic inflammation, which may cause pulmonary vascular dysfunction and ultimate life-threatening Pulmonary Hypertension (PH). The mechanisms involved in the progression of HIV and PH remain unclear. The study of HIV-PH is limited due to the lack of tractable animal models that recapitulate infection and pathobiological aspects of PH. On one hand, mice with humanized immune systems (hu-mice) are highly relevant to HIV research but their suitability for HIV-PH research deserves investigation. On another hand, the Hypoxia-Sugen is a well-established model for experimental PH that combines hypoxia with the VEGF antagonist SU5416. To test the suitability of hu-mice, we combined HIV with either SU5416 or hypoxia. Using right heart catheterization, we found that combining HIV+SU5416 exacerbated PH. HIV infection increases human pro-inflammatory cytokines in the lungs, compared to uninfected mice. Histopathological examinations showed pulmonary vascular inflammation with arterial muscularization in HIV-PH. We also found an increase in endothelial-monocyte activating polypeptide II (EMAP II) when combining HIV+SU5416. Therefore, combinations of HIV with SU5416 or hypoxia recapitulate PH in hu-mice, creating well-suited models for infectious mechanistic pulmonary vascular research in small animals.en-USAttribution 4.0 InternationalHIVHIV-associated pulmonary hypertensionHIV-PHHIV-PH Pulmonary hypertensionEMAP IIHypoxiaSU5416Humanized miceArticle