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 pl...

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Autores principales:	Adam Cornwell, Rohith Palli, Meera V. Singh, Lauren Benoodt, Alicia Tyrell, Jun-ichi Abe, Giovanni Schifitto, Sanjay B. Maggirwar, Juilee Thakar
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/50c82d93ef8840fd8ec8d9ebf2e6750a
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spelling	oai:doaj.org-article:50c82d93ef8840fd8ec8d9ebf2e6750a2021-12-02T14:06:25ZMolecular characterization of atherosclerosis in HIV positive persons10.1038/s41598-021-82429-42045-2322https://doaj.org/article/50c82d93ef8840fd8ec8d9ebf2e6750a2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82429-4https://doaj.org/toc/2045-2322Abstract 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-1β, IL-15, and MIP-1α. IP10 and TNFα 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.Adam CornwellRohith PalliMeera V. SinghLauren BenoodtAlicia TyrellJun-ichi AbeGiovanni SchifittoSanjay B. MaggirwarJuilee ThakarNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Adam Cornwell Rohith Palli Meera V. Singh Lauren Benoodt Alicia Tyrell Jun-ichi Abe Giovanni Schifitto Sanjay B. Maggirwar Juilee Thakar Molecular characterization of atherosclerosis in HIV positive persons
description	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-1β, IL-15, and MIP-1α. IP10 and TNFα 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.
format	article
author	Adam Cornwell Rohith Palli Meera V. Singh Lauren Benoodt Alicia Tyrell Jun-ichi Abe Giovanni Schifitto Sanjay B. Maggirwar Juilee Thakar
author_facet	Adam Cornwell Rohith Palli Meera V. Singh Lauren Benoodt Alicia Tyrell Jun-ichi Abe Giovanni Schifitto Sanjay B. Maggirwar Juilee Thakar
author_sort	Adam Cornwell
title	Molecular characterization of atherosclerosis in HIV positive persons
title_short	Molecular characterization of atherosclerosis in HIV positive persons
title_full	Molecular characterization of atherosclerosis in HIV positive persons
title_fullStr	Molecular characterization of atherosclerosis in HIV positive persons
title_full_unstemmed	Molecular characterization of atherosclerosis in HIV positive persons
title_sort	molecular characterization of atherosclerosis in hiv positive persons
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/50c82d93ef8840fd8ec8d9ebf2e6750a
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Molecular characterization of atherosclerosis in HIV positive persons

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