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Molecular characterization of atherosclerosis in HIV positive persons.

ABSTRACT: People living with HIV are at higher risk of atherosclerosis (AS). The pathogenesis of this risk is not fully understood. To assess the regulatory networks involved in AS we sequenced mRNA of the peripheral blood mononuclear cells (PBMCs) and measured cytokine and chemokine levels in the plasma of 13 persons living with HIV and 12 matched HIV-negative persons with and without AS. microRNAs (miRNAs) are known to play a role in HIV infection and may modulate gene regulation to drive AS. Hence, we further assessed miRNA expression in PBMCs of a subset of 12 HIV+?people with and without atherosclerosis. We identified 12 miRNAs differentially expressed between HIV+?AS+?and HIV+?, and validated 5 of those by RT-qPCR. While a few of these miRNAs have been implicated in HIV and atherosclerosis, others are novel. Integrating miRNA measurements with mRNA, we identified 27 target genes including SLC4A7, a critical sodium and bicarbonate transporter, that are potentially dysregulated during atherosclerosis. Additionally, we uncovered that levels of plasma cytokines were associated with transcription factor activity and miRNA expression in PBMCs. For example, BACH2 activity was associated with IL-1?, IL-15, and MIP-1?. IP10 and TNF? levels were associated with miR-124-3p. Finally, integration of all data types into a single network revealed increased importance of miRNAs in network regulation of the HIV+?group in contrast with increased importance of cytokines in the HIV+?AS+?group.

SUBMITTER: Cornwell A

PROVIDER: S-EPMC7865026 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Molecular characterization of atherosclerosis in HIV positive persons.

Cornwell Adam A Palli Rohith R Singh Meera V MV Benoodt Lauren L Tyrell Alicia A Abe Jun-Ichi JI Schifitto Giovanni G Maggirwar Sanjay B SB Thakar Juilee J

Scientific reports 20210205 1

People living with HIV are at higher risk of atherosclerosis (AS). The pathogenesis of this risk is not fully understood. To assess the regulatory networks involved in AS we sequenced mRNA of the peripheral blood mononuclear cells (PBMCs) and measured cytokine and chemokine levels in the plasma of 13 persons living with HIV and 12 matched HIV-negative persons with and without AS. microRNAs (miRNAs) are known to play a role in HIV infection and may modulate gene regulation to drive AS. Hence, we ...[more]

PMID: 33547350

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Project description:BackgroundPeople with HIV (HIV+) may have increased cardiovascular event rates compared with HIV-negative (HIV-) persons. Cross-sectional data from the United States and Switzerland, based on coronary artery calcium scan (CAC) and coronary computed tomography angiography (CCTA), suggest, respectively, increased and similar prevalence of subclinical atherosclerosis in HIV+ vs HIV- persons.MethodsWe repeated CAC/CCTA in 340 HIV+ and 90 HIV- study participants >2 years after baseline CAC/CCTA. We assessed the association of HIV infection, Framingham risk score (FRS), and HIV-related factors with the progression of subclinical atherosclerosis.ResultsHIV+ were younger than HIV- participants (median age, 52 vs 56 years; P < .01) but had similar median 10-year FRS (8.9% vs 9.0%; P = .82); 94% had suppressed HIV viral load. In univariable and multivariable analyses, FRS was associated with the incidence rate ratio (IRR) of new subclinical atherosclerosis at the follow-up CAC/CCTA, but HIV infection was not: any plaque (adjusted IRR for HIV+ vs HIV- participants, 1.21; 95% CI, 0.62-2.35), calcified plaque (adjusted IRR for HIV+ vs HIV- participants, 1.06; 95% CI, 0.56-2), noncalcified/mixed plaque (adjusted IRR for HIV+ vs HIV- participants, 1.24; 95% CI, 0.69-2.21), and high-risk plaque (adjusted IRR for HIV+ vs HIV- participants, 1.46; 95% CI, 0.66-3.20). Progression of CAC score between baseline and follow-up CAC/CCTA was similar in HIV+ (median annualized change [interquartile range {IQR}], 0.41 [0-10.19]) and HIV- participants (median annualized change [IQR], 2.38 [0-16.29]; P = .11), as was progression of coronary segment severity score (HIV+: median annualized change [IQR], 0 [0-0.47]; HIV-: median annualized change [IQR], 0 [0-0.52]; P = .10) and coronary segment involvement score (HIV+: median annualized change [IQR], 0 [0-0.45]; HIV-: median annualized change [IQR], 0 [0-0.41]; P = .25).ConclusionsIn this longitudinal CAC/CCTA study from Switzerland, Framingham risk score was associated with progression of subclinical atherosclerosis, but HIV infection was not.

Dataset Information

Molecular characterization of atherosclerosis in HIV positive persons.

Publications

Molecular characterization of atherosclerosis in HIV positive persons.

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