BACKGROUND: Chronic inhibition of endothelial nitric oxide (NO) synthesis by the administration of N:(omega)-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)-beta(1) 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-beta(1).
BACKGROUND: Chronic inhibition of endothelial nitric oxide (NO) synthesis by the administration of N:(omega)-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)-beta(1) 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-beta(1).
Authors: Giselle C Meléndez; Jennifer L McLarty; Scott P Levick; Yan Du; Joseph S Janicki; Gregory L Brower Journal: Hypertension Date: 2010-07-06 Impact factor: 10.190
Authors: José L Miguel-Carrasco; Sonia Zambrano; Antonio J Blanca; Alfonso Mate; Carmen M Vázquez Journal: J Inflamm (Lond) Date: 2010-05-12 Impact factor: 4.981
Authors: Sushil K Jain; Thirunavukkarasu Velusamy; Jennifer L Croad; Justin L Rains; Rebeca Bull Journal: Free Radic Biol Med Date: 2009-03-26 Impact factor: 7.376