Effect of chondroitin sulphate in a rabbit model of atherosclerosis aggravated by chronic arthritis.
OBJECTIVE
Among the agents employed to manage osteoarthritis, chondroitin sulphate (CS) is a natural glycosaminoglycan with an anti-inflammatory effect on joint cells. CS might also influence the inflammatory component of atherosclerosis. Our aim was to examine the effect of CS administration on vascular injury and on markers of systemic inflammation in a rabbit model of atherosclerosis aggravated by systemic inflammation provoked by chronic antigen-induced arthritis.


METHODS
Atherosclerosis was induced in rabbits by maintaining them on a hyperlipidaemic diet after producing an endothelial lesion in the femoral arteries. Simultaneously, chronic arthritis was induced in these animals by repeated intraarticular injections of ovalbumin in previously immunized rabbits. A group of these rabbits were treated prophylactically with CS (100 mg kg(-1)day(-1)) and when the animals were killed, serum and peripheral blood mononuclear cells (PBMC) were isolated. Furthermore, femoral arteries and thoracic aorta were used for gene expression studies and histological examination.


RESULTS
CS administration reduced the concentration of the proinflammatory molecules C-reactive protein and IL-6 in serum. Likewise, CS inhibited the expression of CCL2/monocyte chemoattractant protein (MCP)-1 and cyclooxygenase (COX)-2 in PBMC, and reduced the nuclear translocation of nuclear factor-kappaB. In the femoral lesion, CS also diminished the expression of CCL2 and COX-2, as well as the ratio of the intima/media thickness. Moreover, CS decreased the percentage of rabbits with atherosclerosis and chronic arthritis that developed vascular lesions in the aorta.


CONCLUSIONS
These findings suggest that CS treatment may to some extent impede the progression of atherosclerosis.
Joint and Bone Research Unit and Vascular Research Laboratory, Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain.
G
G
Herrero-Beaumont
M E
ME
Marcos
O
O
Sánchez-Pernaute
R
R
Granados
L
L
Ortega
E
E
Montell
J
J
Vergés
J
J
Egido
R
R
Largo
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D001169:Arthritis, Experimental / Q000150:complications*; D050197:Atherosclerosis / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D002097:C-Reactive Protein / Q000187:drug effects / Q000378:metabolism; D018932:Chemokine CCL2 / Q000187:drug effects / Q000378:metabolism; D002809:Chondroitin Sulfates / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D011817:Rabbits
D000893:Anti-Inflammatory Agents; D018932:Chemokine CCL2; D015850:Interleukin-6; D016328:NF-kappa B; D002809:Chondroitin Sulfates; D002097:C-Reactive Protein; D051546:Cyclooxygenase 2