TGFb is active, and correlates with activators of TGFb, 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 b (TGFb) following porcine coronary angioplasty (PTCA), and have correlated this with the expression of potential in vivo activators of TGFb: 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) TGFb were determined using a modified plasminogen activator–inhibitor / luciferase bioassay. Results: Levels of active TGFb significantly increased 2 h to 7 days after angioplasty, compared to non-injured controls. Levels returned to baseline by 28 days. Active TGFb in tissues adjacent to the injured artery did not change. Total TGFb 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 TGFb, that correlates with the expression of TGFb activators. Thus, TGFb is a good potential target for anti-restenotic therapies.  2001 Elsevier Science B.V. All rights reserved.