Antibodies against transforming growth factor-β1 suppress intimal hyperplasia in a rat model

Abstract

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-β1 in a rat carotid artery injury model confirmed the presence of a previously reported increase in TGF-β1 mRNA in the media of injured arteries. Administration of neutralizing anti-TGF-β1 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-β1 group relative to controls (P < 0.01). Immunohistochemical staining showed that two TGF-β1-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-β1-treated animals. We conclude that TGF-β1 is causally involved in the development of intimal hyperplasia, and that anti-TGF-β1 agents may be useful in achieving at least partial control of this condition.