Persistently increased expression of the transforming growth factor-β1 gene in human vascular restenosis: Analysis of 62 patients with one or more episode of restenosis

Transforming growth factor-beta-1 (TGF-β1) is a multifunctional cytokine with both growth-promoting and growth-inhibiting properties. Moreover, there is abundant evidence that TGF-β1 is the principal growth factor responsible for regulating proteoglycan synthesis in human blood vessels. To determine the potential contribution of TGF-β1 to restenosis, the current investigation sought to determine the time course of expression postangioplasty of the TGF-β1 gene. In situ hybridization was performed on tissue specimens obtained by directional atherectomy from 62 patients who had previously undergone angioplasty of native coronary or peripheral arteries and/or saphenous vein bypass grafts. The time interval between angioplasty and atherectomy was 1 hour to 25 months (M ± SEM = 5 ± 4 months) for all 62 patients, 5 ± 4 months for coronary arterial specimens, 8 ± 5 months for vein graft specimens, and 7 ± 3 months for peripheral arterial specimens. TGF-β1 mRNA expression remained persistently increased independent of the site from or time interval following which the specimen was obtained. For saphenous vein by pass grafts, TGF-β1 expression was highest in specimens retreived from patients with multiple versus single episodes of restenosis (16 ± 5 vs. 6 ± 5 grains/nucleus, p < 0.01). TGF-β1 expression did not correlate with patient age, sex, or known risk factors for coronary heart disease. The persistently augmented expression of TGF-β1 observed in the present series of restenosis lesions provides further support for the concept that TGF-β1 influences growth and development of restenosis plaque.