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

Christopher S Wilcox; Carly Herbert; Cheng Wang; Yuchi Ma; Philena Sun; Tian Li; Jennifer Verbesey; Princy Kumar; Seble Kassaye; William J Welch; Michael J Choi; Negiin Pourafshar; Dan Wang

doi:10.1093/infdis/jiae094

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

J Infect Dis. 2024 Mar 1:jiae094. doi: 10.1093/infdis/jiae094. Online ahead of print.

Authors

Christopher S Wilcox¹, Carly Herbert², Cheng Wang^{1

3}, Yuchi Ma¹, Philena Sun¹, Tian Li¹, Jennifer Verbesey⁴, Princy Kumar^{5

6}, Seble Kassaye^{5

6}, William J Welch¹, Michael J Choi¹, Negiin Pourafshar¹, Dan Wang¹

Affiliations

¹ Division of Nephrology and Hypertension and Hypertension Center, Georgetown University, Washington, DC, USA.
² Biostatistician/Data Manager, Multicenter Aids Cohort Study and the Women's Interagency HIV Study (MACS WHIS) Combined Cohort Study, Georgetown University, Washington, DC, USA.
³ Division of Nephrology, The Fifth Hospital of Sun Yat-sen University, Zhuhai, China.
⁴ MedStar Georgetown Transplant Institute, Washington, DC, USA.
⁵ Division of Infection Disease, Georgetown University, Washington, DC, USA.
⁶ Multicenter Aids Cohort Study and the Women's Interagency HIV Study (MACS WIHS), Georgetown University, Washington, DC, USA.

PMID: 38429000
DOI: 10.1093/infdis/jiae094

Abstract

Introduction: People living with the human immunodeficiency virus (PWH) have microvascular disease. Since 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 (+ or -) 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 < 0.05) enhanced acetylcholine (Ach)-induced endothelium dependent relaxation and NO and reduced contractions to thromboxane and endothelin-1. However, these effects of PVAT were reduced significantly (P < 0.05) 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.

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

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