Perivascular Adipose Tissue Inflammation Impairs Microvascular Endothelial Function In People Living With HIV

Introduction and hypothesis: We had reported that people living with HIV (PLWH) have microvascular endothelial dysfunction and increased ROS. We now tested the hypothesis that perivascular adipose tissue (PVAT) could enhance oxidative stress and inflammation and impair the function of subcutaneous microarterioles (SMAs) in PLWH. Methods: SMAs were obtained from young, virally-suppressed HIV-infected subjects (n=11) or matched controls (n=11). Subjects were without associated CVD risk factors. Microvascular reactivity and PVAT function were accessed by myograph from isolated subcutaneous vessels with or without PVAT of skin biopsy. Results: The HIV-infected group had significantly (P<0.05) increased adipose MDA, TNFα, IL-1α, leptin and reduced adiponectin. The PVAT-denuded SMAs from the HIV group had significantly (P<0.05) impaired acetylcholine-induced endothelium-dependent relaxation factor (EDRF, 26±4 vs 38±3%) and NO activity (0.35±0.03 vs 0.58± 0.07 Δfluoresence unit) and significantly (P<0.05) increased contraction to U-46,619 (200±8 vs 141±7%) and endothelin 1 (ET1, 167±12 vs 118±17%) and ROS generation (0.32 ± 0.06 vs 0.1 ± 0.03 (E/DHE fluoresce unit). PVAT enhanced EDRF (50±4 vs 38±3 %) and NO (0.84 ±0.1 vs 0.58±0.07 Δfluoresence unit ) only in controls (P<0.05). The reduction of U46,619 anti-contractivity by PVAT is decreased in HIV (48±7 vs 85±9%, P<0.05). Conclusion: HIV-infected individuals have intrinsic vascular defects from ROS augmented by extrinsic vascular defects from adipose inflammation that impairs the beneficial microvascular PVAT signaling. Therefore, targets for potential prevention of cardiovascular morbidity in PLWH should include the elimination of ROS and inflammation in both microvessels themselves and the surrounding extravascular PVAT.