Circulating miRNA Signatures Associated with Atherosclerosis and Cardiometabolic Comorbidities in People with HIV

Year: 2026

Type: article

Abstract: BACKGROUND: People with HIV (PWH) experience increased cardiovascular disease driven by chronic inflammation despite suppressive antiretroviral therapy. Circulating microRNAs (miRNAs) have emerged as potential biomarkers of cardiometabolic dysfunction, yet their relevance to HIV-associated atherosclerosis remains unclear. METHODS: We analyzed PWH PBMC-derived miRNAs in two independent cohorts: the HUMT cohort (N = 185), characterized by carotid ultrasound assessment of atheroma plaque and carotid intima-media thickness (cIMT), and the CoRIS cohort (N = 119), stratified by cardiometabolic comorbidity burden (≥3 comorbidities vs none). An exploratory miRNA microarray comparing individuals with and without atheroma plaque (AP+ vs. AP-, N = 72) identified candidate miRNAs, a subset of which was selected for validation by RT-qPCR. Associations with atherosclerosis, cardiometabolic comorbidities and the HIV-adapted COMVIH-CoR clinical cardiovascular risk score were examined. RESULTS: Forty-four miRNAs were differentially expressed in AP+ vs. AP- in the microarray. RT-qPCR validation showed sex-specific miRNA association with miR-638 was consistently downregulated in AP+ and pathological cIMT among men, while reduced expression of miR-27b-5p and miR-3613-5p was observed in women. Associations between miRNAs and cardiometabolic comorbidities differed by cohort: in HUMT, miR-638 was reduced in diabetes and obesity, while miR-140-5p and miR-27b-5p were decreased in smokers and individuals with low HDL. CoRIS participants with multiple comorbidities showed a generalized miRNAs upregulation. Notably, miR-140-5p was consistently elevated in individuals with high COMVIH-CoR scores across both cohorts. CONCLUSIONS: PBMC-derived miRNAs capture heterogeneous, context-dependent dimensions of cardiovascular risk in PWH, likely reflecting cumulative immune-metabolic stress rather than universal diagnostic markers of subclinical atherosclerosis and supporting a phenotype-specific role.

Source: Medical Sciences

DOI: 10.3390/medsci14010085

Authors: Marina Martinez-Velasco, José Francisco Sánchez-Herrero, Laura Ibañez, Pablo Velli, Francisco Manuel Muñoz-Lopez, Mireia Cairó, Angeles Jaen, Roser Font, Xavier Martinez-Lacasa, Josep Royo, Joaquim Peraire, Naya Faro-Míguez, Antonio Rivero, Julián Olalla, Pilar Ruiz-Seco, Luis Fernando López-Cortés, Lauro Sumoy, Marta Massanella, David Dalmau

Institutions: IrsiCaixa, University Hospital Mútua de Terrassa, Mútua Terrassa, Universitat de Barcelona, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Instituto de Salud Carlos III, Institut de Recerca Biomèdica Catalunya Sud, Centro de Investigación Biomédica en Red, Hospital Universitari Joan XXIII de Tarragona, Centro de Investigación Biomédica en Red Enfermedades Infecciosas, Universitat Rovira i Virgili, Instituto Maimónides de Investigación Biomédica de Córdoba, Hospital Universitario Reina Sofía, University of Córdoba, Hospital Costa del Sol, Hospital Universitario del Henares, Hospital Universitario Infanta Sofía, Universidad Europea de Madrid, Consejo Superior de Investigaciones Científicas, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío, Universidad de Sevilla

Language: English

Subfield: Emergency Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,689

Funders: Centres de Recerca de Catalunya, Generalitat de Catalunya, Ministerio de Ciencia e Innovación, Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina, Instituto de Salud Carlos III, European Regional Development Fund, Agencia Estatal de Investigación, NextGenerationEU

OpenAlex ID: W7128743000