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- W4313385482 abstract "Abstract Background PAH is a progressive disease of the pulmonary vasculature and right heart, with an increased prevalence in HIV-infected individuals. The causes of HIV-PAH are not known, though evidence suggests immune-mediated pathogenesis. We hypothesize that chronic inflammation contributes to increased pro-inflammatory monocytes and fibrotic alveolar macrophages, which may promote the vascular remodeling characteristic of PAH. We have developed a primate model of simian immunodeficiency virus (SIV)-PAH. This model was used to address the relationship between phenotypic changes in monocyte/macrophage and the development of SIV-PAH. Methods Macaques (n=22) were infected with SIV and serial blood and bronchoalveolar lavage fluid cells were analyzed by flow cytometry. Serial right heart catheterizations were performed to assess mean pulmonary arterial pressure (mPAP). Results Nine macaques showed no change in mPAP over the course of infection, whereas 13 developed PH (mPAP >25mm Hg). Higher frequencies of pro-inflammatory, non-classical monocytes were observed in PH+ animals (p=0.0001), correlating with mPAP (p=0.03). PH- animals had a higher frequency of phagocytic, classical monocytes (p=0.046), negatively correlating with mPAP (p=0.02). PH+ animals had a higher frequency of fibrotic M2a macrophages (p=0.02), correlating with mPAP (p=0.035). PH- animals had a higher frequency of regulatory, M2c macrophages (p=0.0003), negatively correlating with mPAP (p=0.005). Conclusion These results support the hypothesis that HIV-associated PAH is associated with skewing of monocytes and macrophages toward a pro-inflammatory and fibrotic phenotype that contributes to vascular remodeling associated with HIV-PAH." @default.
- W4313385482 created "2023-01-06" @default.
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- W4313385482 date "2016-05-01" @default.
- W4313385482 modified "2023-09-26" @default.
- W4313385482 title "Monocytes and alveolar macrophages skewing in a non-human primate model of HIV-associated pulmonary arterial hypertension (PAH)" @default.
- W4313385482 doi "https://doi.org/10.4049/jimmunol.196.supp.124.33" @default.
- W4313385482 hasPublicationYear "2016" @default.
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