Role of resistin via CAP1 in perivascular adipose tissue and vascular dysfunction in an experimental Arthritis model

• Grant number: 19/24921-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: November 01, 2020
• End date: February 28, 2023
• Field of knowledge: Biological Sciences - Pharmacology - Cardiorenal Pharmacology
• Principal Investigator: Rita de Cassia Aleixo Tostes Passaglia
• Grantee: Aline Garcia Fedoce
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases, AP.CEPID

Abstract

Rheumatoid Arthritis (RA) is a chronic multifactorial inflammatory autoimmune disease of the joints. More than 50% of mortality in RA patients is attributed to Cardiovascular Disease (CVD). Functional and structural changes in Perivascular Adipose Tissue (PVAT), including adipose tissue hyperplasia, increased inflammatory mediators, oxidative stress, decreased adipocyte-derived relaxing factors, and increased proinflammatory adipokines such as resistin, contribute to CVD. In RA increased inflammation and recruitment of M1 and M2 macrophages are observed in the PVAT. Proinflammatory adipokines represent a potential mechanism for PVAT dysfunction in RA. Circulating and synovial resistin concentrations are increased in RA. Human resistin is produced and secreted by monocytes/macrophages and binds to adenylate Cyclase 1-Associated Protein (CAP1) receptors present on the surface of these cells, promoting adipose tissue inflammation with increased release of cytokines, chemokines and immune system cell recruitment, events closely associated with RA. In this context, the involvement of CAP1 resistin in PVAT dysfunction and concomitant vascular dysfunction in RA needs to be investigated, since the mechanisms that mediate PVAT changes are not elucidated. Therefore, in this study we will test the hypothesis that CAP1 resistin contributes to PVAT dysfunction by increasing inflammatory mediators and recruitment of macrophages to this tissue in mice submitted to Adjuvant-Induced Arthritis (AIA). In order to test our hypothesis, we will use C57BL/6 and resistin knockout [Retn (-/-)] mice, with their respective controls, to establish the AIA model. Vascular reactivity assays, enzymatic, molecular and cellular assays will be performed. (AU)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

FEDOCE, Aline Garcia. Role of resistin via CAP1 in the vascular changes mediated by the perivascular adipose tissue in an experimental model of rheumatoid arthritis. 2022. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.