HIV infection induces structural and functional changes in high density lipoproteins. Issue 1 (November 2015)

• Record Type: Journal Article
• Authors: Siegel, Marc O.; Borkowska, Alison G.; Dubrovsky, Larisa; Roth, Mary; Welti, Ruth; Roberts, Afsoon D.; Parenti, David M.; Simon, Gary L.; Sviridov, Dmitri; Simmens, Samuel; Bukrinsky, Michael; Fitzgerald, Michael L.
• Is Part Of: Atherosclerosis. Volume 243:Issue 1(2015)
• Page Start: 19
• Page End: 29
• Publication Date: 2015-11
• Subjects: HIV -- Anti-retroviral treatment -- HDL -- Proteomics -- Lipidomics -- Cholesterol efflux -- PON -- Atherosclerosis; ART anti-retroviral treatment -- CE cholesterol ester -- Cer ceramide -- DSM dihydrosphingomyelin -- ePC etherphosphatidylcholine -- ePS etherphosphatidylserine -- ePE etherphosphatidylethanolamine -- Hex-Cer hexylceramide -- HIV human immunodeficiency virus -- LPE lysophosphatidylethanolamine -- LPC lysophosphatidylcholine -- LXR liver X receptor -- NNRTI non-nucleoside reverse transcriptase inhibitor -- PA phosphatidic acid -- PC phosphatidylcholine -- PE phosphatidylethanolamine -- PCYOX1 Prenylcysteine oxidase 1 -- PI protease inhibitor -- PIn phosphatidylinositol -- PLTP phospholipid transfer protein -- PON paraoxonase -- PS phosphatidylserine -- VCAM vascular cell adhesion molecule -- VL viral load -- TCA trichloroacetic acid.; Arteriosclerosis -- Periodicals; Electronic journals; 616.136
• DOI: 10.1016/j.atherosclerosis.2015.08.036
• Languages: English
• ISSNs: 0021-9150

Abstract

Abstract: Background and aims: Coronary artery disease is a growing clinical problem in HIV-infected subjects. The increased risk of coronary events in this population has been linked to low levels of HDL, but the effects of HIV infection and anti-retroviral treatment (ART) on HDL structure and function remain unknown. Here, we aimed to determine the composition and function of HDL particles isolated from ART-naive and ART-positive HIV-infected patients. Methods and results: Proteomic profiling revealed decreased levels of paraoxonase (PON) 1 and PON 3 in HDL from HIV patients relative to HDL from uninfected controls (p < 0.0001), and PON activity of HDL from control group (0.13 ± 0.01 U/μl) was significantly higher than PON activity of HDL from HIV-infected untreated subjects (0.12 ± 0.01 U/μl, p = 0.0035), subjects treated with non-nucleoside reverse transcriptase inhibitor (NNRTI)-based therapy (0.11 ± 0.01 U/μl, p < 0.0001), subjects treated with protease inhibitor (PI)-based therapy with detectable viral load (0.11 ± 0.01 U/μl, p < 0.0001), and PI-treated patients with undetectable viral load (0.12 ± 0.01 U/μl, p = 0.0164). Lipidomic profiling uncovered a negative correlation between CD4 T cell counts and particle sphingomyelin, lyso-phosphatidylcholine and ether-linked phosphatidylserine content in the ART-naive (R 2 = 0.2611, p < 0.05; R 2 = 0.2722, p < 0.05; and R 2 = 0.3977, p < 0.05, respectively) but not treated HIV-infected subjects. Functional analysis demonstrated a negative correlation between cholesterol efflux capacity of HDL and viral load in the ART-naive HIV-infected group (R 2 = 0.26, p = 0.026). Conclusions: Taken together, these results indicate that HIV infection associates with a number of both protein and lipid compositional changes in HDL particles. Moreover, HIV infection affects cholesterol efflux function of HDL, thus contributing to an increased risk of atherosclerosis in this patient population. Highlights: HDL particles from HIV-infected subjects have reduced PON levels and PON activity. EtherPS levels in HDL from ART-naïve HIV patients correlated with viral load. Cholesterol efflux to HDL from ART-naïve subjects negatively correlated with HIV load. Oxidized LDL were increased in NNRTI-treated patients. Our results indicate remodeling of lipid and protein HDL content in HIV patients.