Background/Purpose: Patients with systemic lupus erythematosus (SLE) are at high risk for cardiovascular disease (CVD) due to accelerated atherosclerosis. lupus patients have more thoracic perivascular adipose tissue (PVAT) than do healthy controls. Moreover, the PVAT in lupus patients exhibits radiographic signs of inflammation and independently associates with aortic calcification scores, a marker of subclinical atherosclerosis. However, mechanisms by which PVAT drives accelerated atherosclerosis in SLE has not been investigated and represent the goal of this study.

Methods:
Mice: 14 weeks old female wild type mice MRL and lupus-prone mice MRL/lpr were utilized according to Augusta University IACUC-approved protocol.

Physiological parameters: body composition was determined using nuclear magnetic resonance (NMR) spectroscopy. Indirect calorimetry test was assessed by a comprehensive laboratory animal monitoring system (CLAMS). Blood pressure was measured by a tail cuff method. Others included glucose tolerance test and measurement of serum lipid panel, adipocytokines and insulin.

Vascular function: Thoracic aortas with or without PVAT from MRL and MRL/lpr mice were harvested and endothelium-dependent and -independent relaxation were assessed by myograph.

Histological study: Thoracic aorta with PVAT were evaluated by staining with Hematoxylin-Eosin, Masson’s Trichrome, Elastin, beige fat marker and leukocyte marker.

Molecular assay: RNA was isolated from thoracic PVAT and RT-qPCR was performed to assess key adipogenic and thermogenic genes, proinflammatory cytokines and leukocyte marker genes.

Results: MRL/lpr mice were similar in weight, but lipodystrophic and hypermetabolic compared to MRL mice. Decreased adiponectin and increased cytokines such as CXCL10, TNFα, IL-1β and IFNγ were noticed in MRL/lpr mice. No differences were noted regarding food consumption, cholesterol, triglycerides, serum insulin, glucose tolerance, or blood pressure. MRL/lpr mice exhibited impaired endothelium-dependent relaxation, which was augmented in the presence of PVAT. In addition, MRL/lpr mice exhibited adipocyte whitening and hypertrophy as well as adventitial hyperplasia. Notably, beige adipose marker was dramatically decreased and leukocyte infiltration was observed in PVAT in MRL/lpr mice. Concordantly, a marked decrease of adipogenesis gene expression accompanied by an increase of pro-inflammatory adipocytokines and leukocyte gene expressions was observed in PVAT of MRL/lpr mice.

Conclusion: Lupus-prone mice with active disease exhibited dysfunctional thoracic PVAT and subsequently promoted vascular dysfunction. Further studies will elucidate interplay between adipocytes and immunity in PVAT microenvironment and how PVAT directly regulate vasculature.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/perivascular-adipose-tissue-promotes-vascular-dysfunction-in-murine-lupus/