We determined the role of high-grade inflammation on endothelial function and its association with biomarkers of endothelial dysfunction in collagen-induced arthritis. Sprague-Dawley rats were divided into a control (n = 12) or collagen-induced arthritis (CIA; n = 21) group. To induce arthritis, Bovine-type-II collagen emulsified in incomplete Freund's adjuvant was injected at the base of the tail. Nine-weeks after the primary immunisation, vascular reactivity in mesenteric and saphenous arteries was assessed using a wire-myograph. Serum concentrations of inflammatory markers (tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), interleukin 1β (IL-1β), C-reactive protein (CRP)) and biomarkers of endothelial dysfunction (vascular cell adhesion molecule-1 (VCAM-1) and asymmetric dimethylarginine (ADMA)) were measured by ELISA. Acetylcholine-induced relaxation in mesenteric and saphenous arteries was impaired in CIA compared to controls (P < 0.05). Responses to sodium nitroprusside were similar between controls and CIA in mesenteric arteries and marginally impaired in saphenous arteries of CIA rats. Compared to controls, TNF-α, IL-6, IL-1β, CRP (all P < 0.00001) and VCAM-1 (P = 0.02) were elevated in CIA. TNF-α (std β(SE) = 0.39(0.16); P = 0.03), IL-6 (std β(SE) = 0.37(0.17); P = 0.03), IL-1β (std β(SE) = 0.41(0.16); P = 0.02) and CRP (std β(SE) = 0.36(0.17); P = 0.04) were associated with VCAM-1. Associations between inflammatory markers and the maximal relaxation (Emax) to acetylcholine in mesenteric arteries were no longer significant after adjusting for VCAM-1 (except for IL-1β). VCAM-1 was inversely associated with the Emax to acetylcholine in mesenteric (std β(SE) = -0.49(0.16); P = 0.01) but not in saphenous arteries (std β(SE) = -0.06(0.18); P = 0.76). In conclusion, exposure to high-grade inflammation impairs endothelial-dependent relaxation. The inflammation-induced increase in VCAM-1 concentrations may contribute to the impaired endothelium-dependent relaxation in mesenteric arteries of CIA rats.
- Biomarkers of endothelial dysfunction
- Collagen-induced arthritis
- Endothelial function