HIV-infected individuals continue to have more extensive cardiovascular disease than expected for their age. While successful therapy can suppress viral load, immune reconstitution is not fully achieved. Some individuals with HIV infection continue to have an activated type 1 interferon (IFN) monocyte profile with circulating low levels of lipopolysaccharide (LPS). We reported that monocytes from HIV-infected subjects have an increase in the major scavenger receptor for lipid uptake and foam cell formation. We also showed that monocytes from HIV infection accumulated more lipids than control uninfected subjects. We hypothesize that activated monocytes from HIV-infected individuals are a risk factor different from HIV-negative subjects with atherosclerosis and carry an activated phenotype that supports modified lipid uptake. Here we show that lipid vesicles called exosomes, secreted from IFN/LPS primed monocytes, can be transferred to human endothelial cells and induce the adhesion molecules ICAM-1 and CCL2 (MCP-1). Monocytes normally secrete exosomes and can transfer miRs, mRNA, cytokines and proteins to other cells including endothelial cells. We will isolate monocyte exosomes from HIV-infected and control individuals to determine their role in endothelial cell activation. We propose to identify what factors in the exosomes induce endothelial cells to promote monocyte adhesion and migration, the initial steps for atherosclerotic plaque formation. Factors identified from monocyte exosomes may present novel targets for treatment that could decrease cardiovascular risk as well as other HIV-associated co-morbidities.
In spite of effective therapy for HIV infection, individuals with HIV experience above average rates of cardiovascular disease. We have identified a potential mechanism related to infection, which accelerates atherosclerotic plaque formation by increasing the number of activated blood cells migrating from the bloodstream into vascular plaques. (End of Abstract)
| Goetzl, Edward J; Goetzl, Laura; Karliner, Joel S et al. (2016) Human plasma platelet-derived exosomes: effects of aspirin. FASEB J 30:2058-63 |
| Tang, Norina; Sun, Bing; Gupta, Archana et al. (2016) Monocyte exosomes induce adhesion molecules and cytokines via activation of NF-?B in endothelial cells. FASEB J 30:3097-106 |
