Role of transforming growth factor-beta1 in cardiovascular inflammatory changes induced by chronic inhibition of nitric oxide synthesis.
We previously reported that chronic inhibition of nitric oxide (NO) synthesis with N(omega)-nitro-L-arginine methyl ester (L-NAME) induces inflammatory changes (monocyte infiltration, myofibroblast formation, and monocyte chemoattractant protein-1 [MCP-1] and transforming growth factor-beta1 [TGF-beta1] expression) in the rat heart and vessel. There is debate regarding whether TGF-beta1 exhibits proinflammatory or anti-inflammatory activities. We used the rat model to investigate the role of TGF-beta in the pathogenesis of such inflammatory changes. We show here that infiltrating monocytes and myofibroblasts in the inflammatory lesions produced TGF-beta1 on the third day of L-NAME administration. Cotreatment with a monoclonal antibody against TGF-beta1, but not with control IgG, prevented the L-NAME-induced cardiac inflammation. The antibody also significantly inhibited the gene expression of MCP-1, P-selectin, and intercellular adhesion molecule-1. In summary, the antibody against TGF-beta1 prevented inflammatory changes in rat heart and vessel induced by chronic inhibition of NO synthesis, suggesting that increased production of TGF-beta1 is involved in the inflammatory changes in this model.
Koyanagi
M
M
Department of Cardiovascular Medicine, Cardiovascular Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Egashira
K
K
Kubo-Inoue
M
M
Usui
M
M
Kitamoto
S
S
Tomita
H
H
Shimokawa
H
H
Takeshita
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D018932:Chemokine CCL2 / Q000235:genetics; D003331:Coronary Vessels / Q000473:pathology / Q000503:physiopathology; D015870:Gene Expression; D006321:Heart / Q000503:physiopathology; D007249:Inflammation / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D008297:Male; D009000:Monocytes / Q000473:pathology / Q000502:physiology; D009206:Myocardium / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis; D019007:P-Selectin / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000502:physiology*
D000911:Antibodies, Monoclonal; D018932:Chemokine CCL2; D019007:P-Selectin; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester