Signals From Inflamed Perivascular Adipose Tissue Contribute to Small-Vessel Dysfunction in Women With Human Immunodeficiency Virus

Abstract

Background: People with the human immunodeficiency virus (PWH) have microvascular disease. Because perivascular adipose tissue (PVAT) regulates microvascular function and adipose tissue is inflamed in PWH, we tested the hypothesis that PWH have inflamed PVAT that impairs the function of their small vessels.

Methods: Subcutaneous small arteries were dissected with or without PVAT from a gluteal skin biopsy from 11 women with treated HIV (WWH) aged < 50 years and 10 matched women without HIV, and studied on isometric myographs. Nitric oxide (NO) and reactive oxygen species (ROS) were measured by fluorescence microscopy. Adipokines and markers of inflammation and ROS were assayed in PVAT.

Results: PVAT surrounding the small arteries in control women significantly (P < .05) enhanced acetylcholine-induced endothelium-dependent relaxation and NO, and reduced contractions to thromboxane and endothelin-1. However, these effects of PVAT were reduced significantly (P < .05) in WWH whose PVAT released less adiponectin but more markers of ROS and inflammation. Moderation of contractions by PVAT were correlated positively with adipose adiponectin.

Conclusions: PVAT from WWH has oxidative stress, inflammation, and reduced release of adiponectin, which may contribute to enhanced contractions and therefore could promote small-artery dysfunction.

Keywords: adiponectin; endothelin-1; inflammation; nitric oxide; reactive oxygen species; thromboxane.

Figure 1.

Mean ± SEM values for acetylcholine-induced endothelium-dependent relaxation (A), endothelium dependent relaxation factor (B), endothelium-dependent hyperpolarization factor (C), and for sodium nitroprusside-induced endothelium-independent relaxation (D) in subcutaneous small arteries comparing vessels from WWH versus women without HIV and vessels with (+) and without (−) PVAT. Abbreviations: NS, not significant; PVAT, perivascular adipose tissue; WWH, women with HIV.

Figure 2.

Mean ± SEM values for contractions to phenylephrine (A), thromboxane (B), endothelin 1 (C), and acetylcholine-induced endothelium-dependent contraction factor (D) comparing vessels from WWH to women without HIV and vessels with (+) and without (−) PVAT. Abbreviations: NAK, high-potassium physiological saline solution plus norepinephrine; NS, not significant; PVAT, perivascular adipose tissue; WWH, women with HIV.

Figure 3.

Mean ± SEM values comparing nitric oxide released by 10⁻⁴ mol · l⁻¹ acetylcholine (A) or reactive oxygen species release by 10⁻⁷ mol · l⁻¹ endothelin 1 (B) from small arteries of WWH and women without HIV with (+) or without (−) PVAT. Abbreviations: DAF-FM, 4-amino-5-methoxyamino-2′,7′-difluorofluorescein diacetate; E/DHE, ethidiumto dihydroethidium ratio; NS, not significant; PVAT, perivascular adipose tissue; WWH, women with HIV.

Figure 4.

Mean ± SEM values for percentage increases in NO generation with acetylcholine and percentage reductions in contractions to U-46619 and ET-1 produced by PVAT comparing vessels from WWH to women without HIV. Abbreviations: ET-1, endothelin 1; NO, nitric oxide; PVAT, perivascular adipose tissue; U-46619, thromboxane; WWH, women with HIV.

Figure 5.

Correlations between individual data for PVAT-induced reductions in contractions to thromboxane (A) and endothelin-1 (B) with PVAT adiponectin levels, and PVAT-induced reductions in contractions to thromboxane (C) and endothelin 1 (D) with PVAT leptin levels using pooled data from women with HIV and women without HIV. Abbreviations: ET-1, endothelin 1; NS, not significant; PVAT, perivascular adipose tissue; U-46619, thromboxane.