TY - JOUR
T1 - Associations of inflammatory markers and vascular cell adhesion molecule-1 with endothelial dysfunction in collagen-induced arthritis
AU - Mokotedi, Lebogang
AU - Millen, Aletta M.E.
AU - Mogane, Conrad
AU - Gomes, Monica
AU - Woodiwiss, Angela J.
AU - Norton, Gavin R.
AU - Michel, Frederic S.
N1 - Funding Information:
This work was supported by the National Research Foundation, the Connective Tissue Diseases Research Fund and the Faculty of Health Sciences Research Committee at the University of the Witwatersrand.
Funding Information:
This work was supported by the National Research Foundation , the Connective Tissue Diseases Research Fund and the Faculty of Health Sciences Research Committee at the University of the Witwatersrand .
Publisher Copyright:
© 2019 Elsevier B.V.
PY - 2019/12/15
Y1 - 2019/12/15
N2 - 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.
AB - 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.
KW - Biomarkers of endothelial dysfunction
KW - Collagen-induced arthritis
KW - Endothelial function
KW - Inflammation
UR - http://www.scopus.com/inward/record.url?scp=85075361176&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2019.172786
DO - 10.1016/j.ejphar.2019.172786
M3 - Article
C2 - 31712060
AN - SCOPUS:85075361176
SN - 0014-2999
VL - 865
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
M1 - 172786
ER -