Molecular characterization of atherosclerosis in HIV positive persons
Open Access
- 5 February 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Scientific Reports
- Vol. 11 (1), 1-14
- https://doi.org/10.1038/s41598-021-82429-4
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 beta, IL-15, and MIP-1 alpha. IP10 and TNF alpha 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.Funding Information
- National Institute of Allergy and Infectious Diseases (P30AI078498, P30AI078498, P30AI078498)
- U.S. National Library of Medicine (F31LM012893)
- National Institute of General Medical Sciences (T32GM07356)
- National Heart, Lung, and Blood Institute (R01HL123346, R01HL123346, R01HL123346, R01HL123346)
This publication has 110 references indexed in Scilit:
- MicroRNA regulation and its effects on cellular transcriptome in Human Immunodeficiency Virus-1 (HIV-1) infected individuals with distinct viral load and CD4 cell countsBMC Infectious Diseases, 2013
- Heart Disease and Stroke Statistics—2012 UpdateCirculation, 2012
- MicroRNAs and human retrovirusesBiochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, 2011
- MicroRNA-10a regulation of proinflammatory phenotype in athero-susceptible endothelium in vivo and in vitroProceedings of the National Academy of Sciences of the United States of America, 2010
- MicroRNA-mediated integration of haemodynamics and Vegf signalling during angiogenesisNature, 2010
- Preclinical atherosclerosis due to HIV infection: carotid intima-medial thickness measurements from the FRAM studyAIDS, 2009
- Association of C-Reactive Protein and HIV Infection With Acute Myocardial InfarctionJAIDS Journal of Acquired Immune Deficiency Syndromes, 2009
- Role of viral replication, antiretroviral therapy, and immunodeficiency in HIV-associated atherosclerosisAIDS, 2009
- miRNA regulation of cytokine genesCytokine, 2009
- Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction NetworksGenome Research, 2003