Role of monocyte chemoattractant protein-1 in cardiovascular remodeling induced by chronic blockade of nitric oxide synthesis

Masamichi Koyanagi, Kensuke Egashira, Shiro Kitamoto, Weihua Ni, Hiroaki Shimokawa, Motohiro Takeya, Teizo Yoshimura, Akira Takeshita

Research output: Contribution to journalArticlepeer-review

106 Citations (Scopus)

Abstract

Background - Chronic inhibition of endothelial nitric oxide (NO) synthesis by the administration of N(ω)-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)-β1 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-β1.

Original languageEnglish
Pages (from-to)2243-2248
Number of pages6
JournalCirculation
Volume102
Issue number18
DOIs
Publication statusPublished - Oct 31 2000

Keywords

  • Cell adhesion molecules
  • Endothelium-derived factors
  • Growth substances
  • Inflammation
  • Proteins
  • Remodeling

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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