Abstract
The capacity of HDL to remove cholesterol from macrophages is inversely associated with the severity of angiographic coronary artery disease. The effect of human immunodeficiency virus (HIV) infection or its treatment on the ability of HDL particles to stimulate cholesterol efflux from human macrophages has never been studied. We evaluated the capacity of whole plasma and isolated HDL particles from HIV-infected subjects (n = 231) and uninfected controls (n = 200), as well as in a subset of 41 HIV subjects receiving highly active antiretroviral therapy (HAART) to mediate cholesterol efflux from human macrophages. Plasma cholesterol efflux capacity was reduced (-12%; P = 0.001) in HIV patients as compared with controls. HIV infection reduced by 27% (P < 0.05) the capacity of HDL subfractions to promote cholesterol efflux from macrophages. We observed a reduced ABCA1-dependent efflux capacity of plasma (-27%; P < 0.0001) from HIV-infected subjects as a result of a reduction in the efflux capacity of HDL3 particles. HAART administration restored the capacity of plasma from HIV patients to stimulate cholesterol efflux from human macrophages (9.4%; P = 0.04). During HIV infection, the capacity of whole plasma to remove cholesterol from macrophages is reduced, thus potentially contributing to the increased coronary heart disease in the HIV population. HAART administration restored the removal of cholesterol from macrophages by increasing HDL functionality.
Highlights
The capacity of HDL to remove cholesterol from macrophages is inversely associated with the severity of angiographic coronary artery disease
We presently demonstrate that human immunodeficiency virus (HIV) infection reduces the capacity of the plasma to mediate cholesterol efflux from human macrophages
Such an alteration in the initial step of the reverse cholesterol transport (RCT) pathway might contribute to an accumulation of cholesterol into resident macrophages within the atherosclerotic plaque and might participate in the increased cardiovascular risk observed in HIV-infected subjects
Summary
The capacity of HDL to remove cholesterol from macrophages is inversely associated with the severity of angiographic coronary artery disease. We evaluated the capacity of whole plasma and isolated HDL particles from HIV-infected subjects (n = 231) and uninfected controls (n = 200), as well as in a subset of 41 HIV subjects receiving highly active antiretroviral therapy (HAART) to mediate cholesterol efflux from human macrophages. During HIV infection, the capacity of whole plasma to remove cholesterol from macrophages is reduced, potentially contributing to the increased coronary heart disease in the HIV population. The capacity of HDL to remove cholesterol from macrophages, representing a metric of HDL function, has been shown to be clinically relevant, as it is strongly and inversely associated with both carotid intima-media thickness and the severity of angiographic coronary artery disease; such observations being independent of HDL-C levels [15]
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