Reduced circulating levels of CXCL14 are associated with cardiovascular damage in people living with HIV.

Abstract

Combined antiretroviral therapy (cART) has improved quality of life of people living with HIV (PLWH). However, alterations in adiposity with concomitant cardiovascular disease (CVD) and circulating systemic disturbances reminiscent of the metabolic syndrome still occur. We recently identified chemokine C-X-C motif ligand 14 (CXCL14) as a brown adipokine involved in M2 macrophage migration to adipose tissues to promote energy expenditure and insulin sensitivity, also exerting cardioprotective actions. Here, we aimed to study CXCL14 regulation and potential association with CVD in PLWH. Serum levels of CXCL14 and adipocytokines of interest were quantified in cohort of 50 cART-treated PLWH and 38 age- and sex-matched controls (50.6 ± 10.1 years, 74.1 % males). Adipose biopsies were extracted for CXCL14 mRNA expression assessment using RT-qPCR. Cardiac computed tomography angiography with contrast-enhanced scan was used to determine atherosclerotic coronary burden, and multivariant models were used to integrate data. CXCL14 circulating levels and mRNA expression in subcutaneous fat were reduced in cART-treated PLWH, especially women. While no association with insulin resistance was observed, circulating CXCL14 negatively correlated with visceral adiposity and tumor necrosis factor alpha (TNFα), fibroblast growth factor 23 (FGF23) and phospholipase A2 Group VII (PLA2G7) levels, and with presence of noncalcified atheromatous plaque in PLWH. This reduction in CXCL14 levels and negative association with inflammation and visceral fat in cART-treated PLWH were reminiscent of its regulation in diabesity. Despite further research is needed, association of circulating CXCL14 with noncalcified atheromatous plaque can result in applications as a novel subclinical biomarker for CVD in PLWH.