Increased monocyte adhesion to aortic endothelium in rats with hyperhomocysteinemia: role of chemokine and adhesion molecules.
OBJECTIVE
The stimulatory effect of homocysteine (Hcy) on monocyte chemoattractant protein (MCP)-1 expression in vitro has been suggested to play an important role in Hcy-mediated atherosclerosis. We investigated whether such a stimulatory effect occurs in vivo, leading to monocyte adhesion to the endothelium.


RESULTS
Sprague-Dawley rats were divided into 4 groups. Hyperhomocysteinemia was induced in 1 group of rats after 4 weeks of a high-methionine diet (serum Hcy levels were 4- to 5-fold higher than levels in control rats). The number of ED-1-positive cells present on the surface of aortic endothelium was significantly elevated in hyperhomocysteinemic rats. There was a significant increase in the expression of MCP-1, vascular cell adhesion molecule-1 (VCAM-1), and E-selectin in the endothelium. Antibodies recognizing MCP-1, VCAM-1, or E-selectin could abolish the enhanced monocyte binding to the aortic endothelium of hyperhomocysteinemic rats. Endothelium-dependent aortic relaxation was impaired in hyperhomocysteinemic rats.


CONCLUSIONS
These results suggest that in the absence of other known risk factors, hyperhomocysteinemia stimulates the expression of MCP-1, VCAM-1, and E-selectin in vivo, leading to increased monocyte adhesion to the aortic endothelium. Such an effect may contribute significantly to the development of atherosclerosis by facilitating monocyte/macrophage infiltration into the arterial wall.
Wang
Guoping
G
Department of Pharmacology, Faculty of Medicine, University of Hong Kong, Hong Kong, China. okarmin@hkucc.hku.hk
Woo
Connie W H
CW
Sung
Fion L
FL
Siow
Yaw L
YL
O
Karmin
K
D000818:Animals; D001013:Aorta, Thoracic / Q000737:chemistry / Q000378:metabolism / Q000503:physiopathology; D001161:Arteriosclerosis / Q000097:blood / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000502:physiology*; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000502:physiology; D018925:Chemokines / Q000502:physiology*; D004032:Diet / Q000009:adverse effects; D004195:Disease Models, Animal; D019040:E-Selectin / Q000096:biosynthesis / Q000502:physiology; D004730:Endothelium, Vascular / Q000737:chemistry / Q000378:metabolism / Q000503:physiopathology*; D006710:Homocysteine / Q000097:blood; D020138:Hyperhomocysteinemia / Q000097:blood / Q000503:physiopathology*; D066298:In Vitro Techniques; D008264:Macrophages / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D008297:Male; D009000:Monocytes / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000267:Tissue Adhesions / Q000378:metabolism* / Q000473:pathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000502:physiology
D015815:Cell Adhesion Molecules; D018932:Chemokine CCL2; D018925:Chemokines; D019040:E-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D006710:Homocysteine