Investigating the impact of platelet-monocyte interactions on HIV-associated vascular disease 3119

Abstract Description People living with HIV (PWH) are more susceptible to vascular disease. To investigate the functional consequences of inflammatory platelet-monocyte complexes (PMCs), which are elevated in PWH and are hypothesized to underly vascular comorbidities, we performed scRNA-seq of monocytes isolated from age-, sex-, and cardiovascular risk score-matched participants categorized based on HIV and atherosclerosis (AS) status (n = 8 per group). Unbiased clustering revealed 10 unique monocyte subsets, two of which were identified as PMCs. PMCs in PWH with AS compared to people living with AS alone (PWAS) revealed an upregulation of genes involved inflammatory responses, lipid metabolism, and cardiovascular function, implying that platelet-monocyte interactions in PWH are not only more prevalent but exhibit stronger transcriptional signatures toward disease processes. To determine the effects of platelets on macrophage differentiation, monocytes and activated platelets were cocultured for seven days. PMC-derived macrophages exhibited increased expression of antigen-presentation molecules CD86 and CD40, reduced expression CD14, and elevated release of TNFα in response to LPS stimulation, results indicative of a pro-inflammatory M1 macrophage phenotype. These findings represent novel insight into platelet-mediated monocyte dysfunction in HIV infection, paving the way to develop targeted therapeutic approaches that address virus-associated vascular disease and related comorbidities. Funding Sources T32AI118689 R01HL160229 Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)