04.06 Alterations to adipose tissue-associated vasculopathology during inflammatory arthritis causes vascular dysfunction in dba/1 mice that is resolved by anti-tnf treatment

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Abstract

Background

The physiological function of adipose tissue is altered by the host’s inflammatory response. The implications for maintaining human health or causing inflammation-associated cardiovascular disease are ill defined. The purpose of this study was to determine morphological and molecular alterations to perivascular adipose tissue (PVAT) that functionally impair normal vascular function during inflammatory arthritis.

Materials and methods

Aorta (PVAT intact), renal and gonadal white adipose tissue (WAT) and brown adipose tissue (BAT) from the inter-scapular region were harvested from mice with established Collagen-induced arthritis (CIA) and age-matched naïve controls. Morphological analyses were undertaken on paraffin-embedded tissue sections. Molecular markers for WAT, BAT and macrophages were measured by qPCR.

Results

Cell number increased significantly by 1.8 fold in all adipose (CIA versus naïve mice). Adipocytes were compressed by CIA and voluminosity was significantly reduced in PVAT (2-fold) and BAT (4-fold) but not WAT. The classical M1 macrophage marker CD11c was significantly increase by CIA together with M2 markers such as Arg1 and CD206 in thoracic PVAT. iNOS expression (M1 marker) was not altered by CIA. Anti-TNF therapy reduced PVAT-associated inflammation and restored impaired constriction responses caused by CIA in excised aortae.

Conclusions

These data, reveal potentially important arthritis-associated mechanisms and tissue changes in PVAT and BAT that may be important in the initiation and progression of cardiovascular disease during inflammatory arthritis. We identify CIA as a relevant model to study the abnormal body composition phenotype that are overrepresented in patients with RA and RA-associated cardiovascular comorbidities.

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