PERSISTENTLY INCREASED EXPRESSION OF THE TRANSFORMING GROWTH-FACTOR-BETA-1 GENE IN HUMAN VASCULAR RESTENOSIS - ANALYSIS OF 62 PATIENTS WITHONE OR MORE EPISODE OF RESTENOSIS

Transforming growth factor-beta-1 (TGF-beta 1) is a multifunctional cy tokine with both growth-promoting and growth-inhibiting properties. Mo reover, there is abundant evidence that TGF-beta 1 is the principal gr owth factor responsible for regulating proteoglycan synthesis in human blood vessels. To determine the potential contribution of TGF-beta 1 to restenosis, the current investigation sought to determine the time course of expression postangioplasty of the TGF-beta 1 gene. In situ h ybridization 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 bypas s 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-beta 1 mRNA expression remained persistently increased independen t of the site from or time interval following which the specimen was o btained. For saphenous vein bypass grafts, TGF-beta 1 expression was h ighest in specimens retreived from patients with multiple versus singl e episodes of restenosis (16 +/- 5 vs. 6 +/- 5 grains/nucleus, p < 0.0 1). TGF-beta 1 expression did not correlate with patient age, sex, or known risk factors for coronary heart disease. The persistently augmen ted expression of TGF-beta 1 observed in the present series of resteno sis lesions provides further support for the concept that TGF-beta 1 i nfluences growth and development of restenosis plaque.