Impaired Endothelial Function and Enhanced Contractility of Microarterioles from Persons Living with Human Immunodeficiency Virus (HIV+) is Mediated by Inflamed Perivascular Adipose Tissue

Abstract

This research investigates the mechanisms that contribute to the enhanced cardiovascular disease (CVD) in HIV+ persons. It tests the hypothesis that perivascular adipose tissue (PVAT) mediates the microvascular dysfunction. Subcutaneous microarterioles were dissected from gluteal skin biopsies from 11 HIV+ and 10 matched control women aged < 50 years who were free of CVD risk factors (except increased BMI). Arterioles were mounted on isometric myographs with or without PVAT. Nitric oxide (NO) and reactive oxygen species (ROS) were measured by fluorescence microscopy. PVAT significantly (P < 0.05) enhanced endothelium‐ dependent relaxation (EDR) and NO with acetylcholine and moderated contractions with thromboxane and endothelin 1 (ET1). But these effects of PVAT were significantly (P < 0.05) diminished in HIV+ vs control subjects. Although microarterioles from HIV+ had enhanced ROS with ET1. ROS was not affected by PVAT. Incubated PVAT from HIV+ persons released significantly (P < 0.05) more leptin (47 +/‐ 8 vs 22 +/‐ 3 ng · mg‐1) and less adiponectin (3.0 +/‐ 0.4 vs 4.6 +/‐ 0.5 µg · mg‐1) but more 8‐isoprostane F2α (2.5 +/‐ 0.4 vs 1.3 +/‐ 0.3 µmol · mg‐1) and inflammatory cytokines such as TNFα (11 +/‐ 1 vs 5 +/‐ 1 pg · mg‐1).ConclusionPVAT from young HIV+ women has enhanced oxidative stress and inflammation and impaired ability to enhance microarteriolar NO and moderated contractility. Thus, PVAT and adipokines should be novel foci for therapy to reduce CVD in HIV+ persons.