TGF beta is active, and correlates with activators of TGF beta, following porcine coronary angioplasty

Objective: Restenosis following angioplasty involves processes that may be influenced by local production of cytokines. We investigated the expression of active and total transforming growth factor beta (TGF beta) following p orcine coronary angioplasty (PTCA), and have correlated this with the expre ssion of potential in vivo activators of TGF beta: mannose-6-phosphate/insu lin-like growth factor-II (M6P/IGF-II) receptor and thrombospondin-1. Metho ds: Oversized porcine PTCA was performed and the arteries excised after sel ected intervals. Levels of in situ active and total (active plus latent) TG F beta were determined using a modified plasminogen activator-inhibitor I l uciferase bioassay. Results: Levels of active TGF beta significantly increa sed 2 h to 7 days after angioplasty, compared to non-injured controls. Leve ls returned to baseline by 28 days. Active TGF beta in tissues adjacent to the injured artery did not change. Total TGF beta was significantly higher than controls 2-6 h after injury. M6P/IGF-II receptor mRNA was upregulated between 6 h and 3 days after injury, with protein detectable at 3-28 days. Thrombospondin-1 was detected between 1 h and 14 days. Conclusions: We conc lude that balloon injury causes an early rapid increase in levels of active TGF beta, that correlates with the expression of TGF beta activators. Thus , TGF beta is a good potential target for anti-restenotic therapies. (C) 20 01 Elsevier Science B.V. All rights reserved.