(Circulation. 2000;102:2243.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
Role of Monocyte Chemoattractant Protein-1 in Cardiovascular Remodeling Induced by Chronic Blockade of Nitric Oxide Synthesis
From the Department of Cardiovascular Medicine (M.K., K.E., S.K., W.N., H.S., A.T.), Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; the Second Department of Pathology (M.T.), Kumamoto University School of Medicine, Kumamoto, Japan; and the Immunopathology Section (T.Y.), Laboratory of Immunobiology, National Cancer Institute, Frederick, Md.
Correspondence to Kensuke Egashira, MD, PhD, Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. E-mail egashira{at}cardiol.med.kyushu-u.ac.jp
Background—Chronic inhibition of
endothelial nitric oxide (NO) synthesis by the
administration of
N
-nitro-L-arginine methyl
ester (L-NAME) to rats induces early vascular inflammatory changes
(monocyte infiltration into coronary vessels and monocyte
chemoattractant protein-1 [MCP-1] expression) as well as subsequent
arteriosclerosis (medial thickening and
perivascular fibrosis) and cardiac fibrosis. However, the role of MCP-1
in this process is not known.
Methods and Results—We investigated the effect of a specific monoclonal anti–MCP-1 neutralizing antibody in rats treated with L-NAME to determine the role of monocytes in the regulation of cardiovascular remodeling. We found increased expression of MCP-1 mRNA in vascular endothelial cells and monocytes in inflammatory lesions. Cotreatment with an anti–MCP-1 antibody, but not with control IgG, prevented the L-NAME–induced early inflammation and reduced late coronary vascular medial thickening. In contrast, the anti–MCP-1 antibody did not decrease the development of perivascular fibrosis, the expression of transforming growth factor (TGF)-ß1 mRNA, or systolic pressure overload induced by L-NAME administration.
Conclusions—These results suggest that MCP-1 is necessary for the development of medial thickening as well as monocyte recruitment. In contrast, the pathogenesis of fibrosis may involve other factors, such as TGF-ß1.
Key Words: endothelium-derived factors • remodeling • growth substances • inflammation • cell adhesion molecules • proteins
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