Perivascular adipose tissue promotes vascular dysfunction in murine lupus

Area of Science:

• Cardiovascular research
• Immunology
• Adipose tissue biology

Background:

• Systemic lupus erythematosus (SLE) patients have increased cardiovascular disease (CVD) risk due to accelerated atherosclerosis.
• Thoracic aortic perivascular adipose tissue (PVAT) is linked to vascular calcification in SLE patients.
• The role of PVAT in SLE pathogenesis remains unclear.

Purpose of the Study:

• To investigate the phenotype and function of PVAT in lupus mouse models.
• To elucidate mechanisms linking PVAT and vascular dysfunction in lupus.

Main Methods:

• Utilized mouse models of lupus.
• Performed wire myography to assess vascular function.
• Analyzed PVAT phenotype, including adipocyte morphology, immune cell infiltration, and gene expression.

Main Results:

• Lupus mice displayed hypermetabolism and partial lipodystrophy with PVAT sparing.
• Thoracic aortas from lupus mice showed impaired endothelium-dependent relaxation, worsened by PVAT.
• Lupus PVAT exhibited adipocyte hypertrophy, "whitening," immune cell infiltration, decreased UCP1, and increased inflammatory markers.

Conclusions:

• Dysfunctional and inflamed PVAT in lupus mice contributes to vascular impairment.
• Altered PVAT may play a role in the accelerated atherosclerosis observed in SLE patients.
• Targeting PVAT dysfunction could be a therapeutic strategy for CVD in SLE.