Antibodies against transforming growth factor-beta 1 suppress intimal hyperplasia in a rat model.
Intimal hyperplasia is induced by therapeutic vascular interventions and often results in clinically important narrowing of the vascular lumen. Examination of the role of TGF-beta 1 in a rat carotid artery injury model confirmed the presence of a previously reported increase in TGF-beta 1 mRNA in the media of injured arteries. Administration of neutralizing anti- TGF-beta 1 antibodies significantly (P < 0.05) reduced the size of the intimal lesions that developed after carotid balloon injury. A control antibody had no effect. The intimal/medial area ratio was also reduced in the anti-TGF-beta 1 group relative to controls (P < 0.01). Immunohistochemical staining showed that two TGF-beta 1-induced extracellular matrix components, EDA + fibronectin and versican, were greatly increased in the untreated neointimal lesions, but were almost completely absent from the lesions of the anti-TGF-beta 1-treated animals. We conclude that TGF-beta 1 is causally involved in the development of intimal hyperplasia, and that anti-TGF-beta 1 agents may be useful in achieving at least partial control of this condition.
Wolf
Y G
YG
Cancer Research Center, La Jolla Cancer Research Foundation, California 92037.
Rasmussen
L M
LM
Ruoslahti
E
E
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D001483:Base Sequence; D002455:Cell Division; D005109:Extracellular Matrix / Q000378:metabolism; D006965:Hyperplasia; D008297:Male; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000502:physiology*
D000906:Antibodies; D016212:Transforming Growth Factor beta