TGFβ is active, and correlates with activators of TGFβ, 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 porcine coronary angioplasty (PTCA), and have correlated this with the expression of potential in vivo activators of TGF beta: mannose-6-phosphate/insulin-like growth factor-II (M6P/IGF-II) receptor and thrombospondin-1. Methods: Oversized porcine PTCA was performed and the arteries excised after selected intervals. Levels of in situ active and total (active plus latent) TGF beta were determined using a modified plasminogen activator-inhibitor I luciferase bioassay. Results: Levels of active TGF beta significantly increased 2 h to 7 days after angioplasty, compared to non-injured controls. Levels 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 conclude 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) 2001 Elsevier Science B.V. All rights reserved.