HIV and Drug Use: A Tale of Synergy in Pulmonary Vascular Disease Development

Cook, Christine M.; Craddock, Vaughn; Ram, Anil Kumar; Abraham, A. S.; Dhillon, Navneet K.

doi:10.1002/cphy.c210049

Cited by 1 publication

(2 citation statements)

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“…Pulmonary hypertension, which is defined by elevated pressure in the peripheral pulmonary arteries and failure of the right ventricle, is caused by vasoconstriction and progressive blockage of the distal pulmonary arteries [ 1 ]. The risk of developing pulmonary hypertension in PLWH is 300–6000-fold more than in individuals without HIV infection [ 2 ]. The reports on the impact of antiretroviral therapy on HIV-PH continue to be contradictory, and individuals who have HIV-PH often die from the illness [ 3 , 4 ], thereby making HIV-PH one of the most serious non-infectious consequences of HIV infection [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

“…The reports on the impact of antiretroviral therapy on HIV-PH continue to be contradictory, and individuals who have HIV-PH often die from the illness [ 3 , 4 ], thereby making HIV-PH one of the most serious non-infectious consequences of HIV infection [ 5 ]. Further, illicit drug use increases HIV transmission, disease progression, and non-compliance with ART, particularly in older people with pulmonary hypertension This “double hit” increases the risk of HIV-associated pulmonary hypertension (HIV-PH) and right heart failure [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

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Analysis of MicroRNA Cargo in Circulating Extracellular Vesicles from HIV-Infected Individuals with Pulmonary Hypertension

Mahajan,

Gunewardena,

Morris

et al. 2024

Cells

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The risk of developing pulmonary hypertension (PH) in people living with HIV is at least 300-fold higher than in the general population, and illicit drug use further potentiates the development of HIV-associated PH. The relevance of extracellular vesicles (EVs) containing both coding as well as non-coding RNAs in PH secondary to HIV infection and drug abuse is yet to be explored. We here compared the miRNA cargo of plasma-derived EVs from HIV-infected stimulant users with (HIV + Stimulants + PH) and without PH (HIV + Stimulants) using small RNA sequencing. The data were compared with 12 PH datasets available in the GEO database to identify potential candidate gene targets for differentially altered miRNAs using the following functional analysis tools: ingenuity pathway analysis (IPA), over-representation analysis (ORA), and gene set enrichment analysis (GSEA). MiRNAs involved in promoting cell proliferation and inhibition of intrinsic apoptotic signaling pathways were among the top upregulated miRNAs identified in EVs from the HIV + Stimulants + PH group compared to the HIV + Stimulants group. Alternatively, the downregulated miRNAs in the HIV + Stimulants + PH group suggested an association with the negative regulation of smooth muscle cell proliferation, IL-2 mediated signaling, and transmembrane receptor protein tyrosine kinase signaling pathways. The validation of significantly differentially expressed miRNAs in an independent set of HIV-infected (cocaine users and nondrug users) with and without PH confirmed the upregulation of miR-32-5p, 92-b-3p, and 301a-3p positively regulating cellular proliferation and downregulation of miR-5571, -4670 negatively regulating smooth muscle proliferation in EVs from HIV-PH patients. This increase in miR-301a-3p and decrease in miR-4670 were negatively correlated with the CD4 count and FEV1/FVC ratio, and positively correlated with viral load. Collectively, this data suggest the association of alterations in the miRNA cargo of circulating EVs with HIV-PH.

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