THE TEMPORAL EXPRESSION OF TRANSFORMING GROWTH FACTOR-BETA(1) IN EARLY AORTOCORONARY VEIN GRAFTS

The success of coronary reconstructive procedures is limited by the hi gh incidence of restenosis secondary to intimal hyperplasia (IH). Tran sforming growth factor-beta(1) (TGF-beta(1)) is a growth factor which has been shown to be important in the early development of IH in arter ies and peripheral vein grafts. To date, there is little information c oncerning the early remodeling in aortocoronary vein grafts (ACVG). Th e purpose of this study was to characterize the expression of TGF-beta (1), expression in early aortocoronary vein grafts. Eighteen mongrel d ogs underwent aortocoronary vein bypass grafting. Vein grafts were exc ised at 2 hr, 4 hr, and 7 days after implantation, snap frozen, and pr ocessed for ribonuclease protection assays (RPA) using P-32-labeled ri boprobes for TGF-beta(1) and 18 S rRNA. TGF-beta(1) expression was qua ntified by densitometric analysis of autoradiographs which were expres sed as a ratio TGF-beta(1)/rRNA. Representative vessel rings were also collected for histology, There was a significant rise in TGF-beta(1) expression in the 2-hr vein grafts (0.42 +/- 0.04 compared to control saphenous vein 0.21 +/- 0.05, P < 0.02). In addition, there was signif icant downregulation of TGF-beta(1) at 4 hr (0.28 +/- 0.05) and at 7 d ays (0.18 +/- 0.01) when compared to 2 hr (P < 0.05). Histological spe cimens showed minimal intimal hyperplasia at 7 days. These results sho w for the first time an acute rise in TGF-beta(1) expression in ACVG. This upregulation quickly subsides by 4 hr and gene expression approac hes control values by 7 days, By understanding this temporal relations hip of expression one could better target potential therapeutic modali ties to attenuate IH. (C) 1997 Academic Press.