We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Perivascular adipose tissue promotes vascular dysfunction in murine lupus.
- Authors
Hong Shi; Goo, Brandee; Kim, David; Kress, Taylor C.; Ogbi, Mourad; Mintz, James; Hanping Wu; de Chantemèle, Eric J. Belin; Stepp, David; Xiaochun Long; Guha, Avirup; Lee, Richard; Carbone, Laura; Annex, Brian H.; Hui, David Y.; Ha Won Kim; Weintraub, Neal L.
- Abstract
Introduction: Patients with systemic lupus erythematosus (SLE) are at elevated risk for Q10 cardiovascular disease (CVD) due to accelerated atherosclerosis. Compared to heathy control subjects, lupus patients have higher volumes and densities of thoracic aortic perivascular adipose tissue (PVAT), which independently associates with vascular calcification, a marker of subclinical atherosclerosis. However, the biological and functional role of PVAT in SLE has not been directly investigated. Methods: Using mouse models of lupus, we studied the phenotype and function of PVAT, and the mechanisms linking PVAT and vascular dysfunction in lupus disease. Results and discussion: Lupus mice were hypermetabolic and exhibited partial lipodystrophy, with sparing of thoracic aortic PVAT. Using wire myography, we found that mice with active lupus exhibited impaired endothelium-dependent relaxation of thoracic aorta, which was further exacerbated in the presence of thoracic aortic PVAT. Interestingly, PVAT from lupus mice exhibited phenotypic switching, as evidenced by "whitening" and hypertrophy of perivascular adipocytes along with immune cell infiltration, in association with adventitial hyperplasia. In addition, expression of UCP1, a brown/beige adipose marker, was dramatically decreased, while CD45-positive leukocyte infiltration was increased, in PVAT from lupus mice. Furthermore, PVAT from lupus mice exhibited a marked decrease in adipogenic gene expression, concomitant with increased pro-inflammatory adipocytokine and leukocyte marker expression. Taken together, these results suggest that dysfunctional, inflamed PVAT may contribute to vascular disease in lupus.
- Subjects
ADIPOSE tissues; BIOMARKERS; SYSTEMIC lupus erythematosus; THORACIC aorta; ARTERIAL calcification
- Publication
Frontiers in Immunology, 2023, Vol 14, p1
- ISSN
1664-3224
- Publication type
Article
- DOI
10.3389/fimmu.2023.1095034