Abstract P623: Endothelial Dysfunction and Abnormal Perivascular Adipose Tissue Signaling in Subcutaneous Vessels from HIV-infected individuals

Objective: Perivascular adipose tissue (PVAT) normally promotes vascular endothelial function, whereas is impaired by reactive oxygen species (ROS) in CVD. But PVAT effects on microvessels in HIV are unexplored. We previously reported endothelial dysfunction in living subcutaneous microvascular arterioles (SMAs) dissected from a gluteal biopsy in HIV infected individuals. We test hypothesis that HIV increases microvascular ROS and asymmetric dimethylarginine (ADMA) leading to impair microvascular function and PVAT signaling. Methods: Isolated SMAs with or without PVAT were prepared from young African American HIV-infected (n=8) and matched HIV-uninfected women (n=6) enrolled in the DC Women’s Interagency HIV Study (DC-WIHS). HIV-infected participants were virally suppressed on HAART without identified CVD risk factors (except obesity). SMA’s acetylcholine (ACh)-induced endothelium dependent relaxation (EDR), nitric oxide (NO) activity (DAF-FM), ACh-induced endothelium dependent contractions (EDC) and ROS generation (temp-9AC), plasma L-arginine, ADMA and adipose adipokines and malondialdehyde (MDA) were measured. Results: HIV-infected participants had significantly ( p <0.05) reduced plasma ratio of L-arginine : ADMA (99 ± 13 vs 182 ± 32 μmol/μmol), increased adipose MDA (15.1 ± 2.5 vs 10.9 ± 2.6 ng/mg protein) and leptin (40 ± 9 vs 28 ± 7 ng/mg protein); and reduced adiponectin in plasma (14 ± 2 vs 23 ± 2 ng/ml) and in adipose (2.1 ± 0.3 vs 4.6 ± 1.3 ng/mg protein). ACh-induced EDR (57 ± 4 vs 71± 4%) and NO (0.20 ± 0.03 vs 0.58 ± 0.07 Δfluoresce unit) were significantly attenuated (p<0.05) in vessels from HIV-infected participants, whereas EDC (22 ± 2 vs 7 ± 2%) and O 2 - (0.17 ± 0.02 vs 0.09 ± 0.02 Δfluoresce unit) were significantly increased ( p <0.05) . PVAT significantly increased ( p <0.05) EDR (87 ± 3 vs 72 ± 4%) and NO (0.84 ± 0.09 vs 0.58 ± 0.08 Δfluoresce unit) only in control vessels. Conclusion: HIV-infected individuals have reductions in NO synthase substrate: inhibitor ratio (L-arginine:ADMA) and consequent increased intrinsic vascular effects of ROS leading to disruption of the beneficial microvascular PVAT signaling pathway. Therapeutic targets for vascular dysfunction in HIV should include ROS and its extravascular actions on ADMA and PVAT.