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

Author:

Wilcox Christopher S1,Herbert Carly2,Wang Cheng13,Ma Yuchi1,Sun Philena1,Li Tian1,Verbesey Jennifer4,Kumar Princy56,Kassaye Seble56,Welch William J1,Choi Michael J17,Pourafshar Negiin17,Wang Dan1

Affiliation:

1. Division of Nephrology and Hypertension, Georgetown University , Washington, District of Columbia , USA

2. Multicenter Aids Cohort Study and the Women's Interagency HIV Study Combined Cohort Study, Georgetown University , Washington, District of Columbia , USA

3. Division of Nephrology, The Fifth Hospital of Sun Yat-sen University , Zhuhai , China

4. MedStar Georgetown Transplant Institute , Washington, District of Columbia , USA

5. Division of Infection Disease, Georgetown University , Washington, District of Columbia , USA

6. Multicenter Aids Cohort Study and the Women's Interagency HIV Study, Georgetown University , Washington, District of Columbia , USA

7. Medstar Georgetown University Hospital , Department of Nephrology and Hypertension, Washington, District of Columbia , USA

Abstract

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.

Funder

National Institutes of Health

Gildenhorn-Spiesman Family Foundation

Georgetown University

Marriott Family Research Award

National Heart, Lung, and Blood Institute

National Institute of Allergy and Infectious Diseases

National Center for Advancing Translational Science

Department of Medicine

Publisher

Oxford University Press (OUP)

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