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Circulating MicroRNAs Related to Arterial Stiffness in Adults with HIV Infection
Sideris Nanoudis1, Maria P Yavropoulou1, Olga Tsachouridou1
11st Internal Medicine Department, AHEPA University Hospital, School of Medicine, Aristotle University of Thessaloniki, 55436 Thessaloniki, Greece.
Abstract:
People with HIV (PWH) have an elevated risk of cardiovascular disease compared to those without HIV. This study aimed to investigate the relative serum expression of microRNAs (miRNAs) associated with arterial stiffness, a significant marker of cardiovascular disease. A total of 36 male PWH and 36 people without HIV, matched for age, body mass index, pack years, and dyslipidemia, were included in the study. Participants with a history of hypertension, diabetes mellitus, cardiovascular disease, cancer, or intravenous drug use were excluded. Markers of arterial stiffness, including carotid-femoral pulse wave velocity (cfPWV) and augmentation index adjusted to 75 beats per minute (AIx@75), were measured via applanation tonometry. We analyzed the relative expression of 11 circulating miRNAs using real-time PCR: let-7b-5p, miR-19b-3p, miR-21-5p, miR-29a-3p, miR-126-3p, miR-130a-3p, miR-145-5p, miR-181b-5p, miR-221-3p, miR-222-3p, and miR-223-3p. cfPWV was significantly higher in PWH compared to people without HIV (9.3 vs. 8.6 m/s, p = 0.019), while AIx@75, peripheral, and aortic blood pressures did not differ among groups. The relative expression of circulating miRNAs was significantly higher in PWH compared to controls for let-7b-5p (fold change: 5.24, p = 0.027), miR-21-5p (fold change: 3.41, p < 0.001), miR-126-3p (fold change: 1.23, p = 0.019), and miR-222-3p (fold change: 3.31, p = 0.002). Conversely, the relative expression of circulating miR-19b-3p was significantly lower in PWH (fold change: 0.61, p = 0.049). Among HIV-related factors, the nadir CD4+T-cell count of <200 cells/mm3 was independently associated with the relative expression of circulating let-7b-5p (β = 0.344, p = 0.049), while current non-nucleoside reverse transcriptase inhibitor (NNRTI) treatment was independently associated with the relative expression of circulating miR-126-3p (β = 0.389, p = 0.010). No associations were found between the duration of HIV infection or the duration of ART and the serum miRNA expression. This study highlights a distinct circulating miRNA profile in PWH with higher cfPWV compared to those without HIV, which may contribute to increased arterial stiffness.
Insights
People with HIV (PWH) show increased arterial stiffness, indicated by higher carotid-femoral pulse wave velocity (cfPWV). Distinct circulating microRNA (miRNA) profiles are observed in PWH, potentially contributing to cardiovascular disease risk.
Area of Science:
- Cardiovascular disease research
- HIV/AIDS research
- Molecular biology and genetics
Background:
- People with HIV (PWH) have a higher risk of cardiovascular disease (CVD).
- Arterial stiffness is a key indicator of CVD and is elevated in PWH.
- MicroRNAs (miRNAs) are implicated in cardiovascular health and disease.
Purpose of the Study:
- To investigate the serum expression of specific microRNAs (miRNAs) linked to arterial stiffness in people with HIV (PWH).
- To compare arterial stiffness markers and circulating miRNA profiles between PWH and HIV-negative individuals.
- To explore associations between HIV-related factors and miRNA expression.
Main Methods:
- Study included 36 male PWH and 36 matched HIV-negative controls.
- Arterial stiffness measured using carotid-femoral pulse wave velocity (cfPWV) and augmentation index (AIx@75).
- Relative expression of 11 circulating miRNAs analyzed via real-time PCR.
Main Results:
- PWH exhibited significantly higher cfPWV compared to controls (9.3 vs. 8.6 m/s, p=0.019).
- Elevated serum levels of let-7b-5p, miR-21-5p, miR-126-3p, and miR-222-3p were found in PWH.
- Lower miR-19b-3p expression was observed in PWH; nadir CD4+ count and non-nucleoside reverse transcriptase inhibitor (NNRTI) treatment associated with specific miRNA levels.
Conclusions:
- PWH demonstrate a distinct circulating miRNA profile associated with increased arterial stiffness.
- Specific miRNAs (let-7b-5p, miR-21-5p, miR-126-3p, miR-222-3p) may play a role in HIV-associated CVD.
- Findings suggest potential miRNA-based biomarkers for cardiovascular risk in PWH.

