Expression of IGF-1, IGF-1 receptor and TGF-beta following balloon angioplasty in atherosclerotic and normal rabbit iliac arteries: An immunocytochemical study

Growth factors have been implicated in the pathogenesis of restenosis (myoi ntimal hyperplasia after coronary interventions). In this study, we examine d the expression of insulin-like growth factor-I (IGF-1), IGF-1 receptor, a nd transforming growth factor-beta (TGF-beta) in atherosclerotic and normal rabbit iliac arteries following overstretch balloon angioplasty of the ili ac arteries to create a vascular lesion. Animals were sacrificed at 0, 3, 7 , 15 and 42 days post angioplasty. The iliac arteries were processed for im munocytochemical localization of IGF-1, IGF-1 receptor and TGF-beta using c olloidal gold and the data were quantitatively analyzed. IGF-1, IGF-1 recep tor and TGF-beta immunoreactivity were all significantly increased in ather osclerotic arteries compared to control at all of the time points examined. Following balloon angioplasty, the levels of IGF-1 and IGF-1 receptor incr eased significantly in both control and even further in hypercholesterolemi c vessels. In control vessels, the IGF-1 levels returned to preintervention levels, while in atherosclerotic vessels, the levels of IGF-1 and IGF-1 re ceptor remained elevated. In addition, TGF-beta levels in control vessels s howed an initial rise in the first week following injury but then returned to baseline levels. In contrast, atherosclerotic vessels demonstrated a sus tained expression of TGF-beta. Thus, IGF-1 and TGF-beta expression is diffe rent in normal vs. atherosclerotic vessels following vascular injury. The i ntensity of expression of IGF-1 and its receptor, which is not reduced at 4 2 days compared to 15 days following injury, support a role for IGF-1 in sm ooth muscle cell proliferation and migration. The sustained increase in TGF -beta could facilitate extracellular matrix (ECM) accumulation. Local vascu lar therapy that is directed towards modulating the effects of IGF-1 and TG F-beta could reduce restenosis. (C) 1999 Elsevier Science B.V. All rights r eserved.