Mice with humanized immune system as novel models to study HIV-associated pulmonary hypertension
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2022Metadata
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Rodríguez Irizarry, Valerie J.
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Mice with humanized immune system as novel models to study HIV-associated pulmonary hypertension
Author
- Rodríguez Irizarry, Valerie J.;
- Schneider, Alina C.;
- Ahle, Daniel;
- Smith, Justin M.;
- Suárez Martínez, Edu B.;
- Salazar, Ethan A.;
- McDaniel Mims, Brianyell;
- Rasha, Fahmida;
- Moussa, Hanna;
- Moustaïd Moussa, Naima;
- Pruitt, Kevin;
- Fonseca, Marcelo;
- Henríquez Luna, Mauricio Gabriel;
- Clauss, Matthias A.;
- Grisham, Matthew B.;
- Almodóvar, Sharilyn;
Abstract
People 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.
Patrocinador
nited States Department of Health & Human Services
National Institutes of Health (NIH) - USA
NIH National Heart Lung & Blood Institute (NHLBI) R21 HL129852
United States Department of Health & Human Services
National Institutes of Health (NIH) - USA R25 GM096955
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Front. Immunol. 13:936164 (2022)
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