Regulatory Peptides 79 (1999) 47–53 Expression of IGF-1, IGF-1 receptor and TGF-b following balloon angioplasty in atherosclerotic and normal rabbit iliac arteries: An immunocytochemical study a, a a b * Maria B. Grant , Thomas J. Wargovich , David M. Bush , Denifield W. Player , a c a Sergio Caballero , Marie Foegh , Polyxenie E. Spoerri a Department of Medicine, College of Medicine, University of Florida, Gainesville, FL 32610, USA b Department of Anatomy and Cell Biology, College of Medicine, University of Florida, Gainesville, FL 32610, USA c Department of Surgery, College of Medicine, Georgetown University, Washington, DC 20007, USA Received 10 January 1998; received in revised form 22 March 1998; accepted 10 April 1998 Abstract Growth factors have been implicated in the pathogenesis of restenosis (myointimal hyperplasia after coronary interventions). In this study, we examined the expression of insulin-like growth factor-I (IGF-1), IGF-1 receptor, and transforming growth factor-b (TGF-b) in atherosclerotic and normal rabbit iliac arteries following overstretch balloon angioplasty of the iliac 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 immunocytochemical localization of IGF-1, IGF-1 receptor and TGF-b using colloidal gold and the data were quantitatively analyzed. IGF-1, IGF-1 receptor and TGF-b immunoreactivity were all significantly increased in atherosclerotic arteries compared to control at all of the time points examined. Following balloon angioplasty, the levels of IGF-1 and IGF-1 receptor increased significantly in both control and even further in hypercholesterolemic vessels. In control vessels, the IGF-1 levels returned to preintervention levels, while in atherosclerotic vessels, the levels of IGF-1 and IGF-1 receptor remained elevated. In addition, TGF-b levels in control vessels showed an initial rise in the first week following injury but then returned to baseline levels. In contrast, atherosclerotic vessels demonstrated a sustained expression of TGF-b. Thus, IGF-1 and TGF-b expression is different in normal vs. atherosclerotic vessels following vascular injury. The intensity of expression of IGF-1 and its receptor, which is not reduced at 42 days compared to 15 days following injury, support a role for IGF-1 in smooth muscle cell proliferation and migration. The sustained increase in TGF-b could facilitate extracellular matrix (ECM) accumulation. Local vascular therapy that is directed towards modulating the effects of IGF-1 and TGF-b could reduce restenosis.  1999 Elsevier Science B.V. All rights reserved. Keywords: Myointimal hyperplasia; Restenosis; Atherosclerosis; Growth factors 1. Introduction gioplasty are accompanied by a high rate of restenosis [1]. Restenosis could be considered an excessive repair process Percutaneous transluminal coronary angioplasty is a or an accelerated response to injury of smooth muscle cells standard therapeutic technique for reducing obstructive in atherosclerotic vessels [2]. Growth factors stimulate lesions and improving blood flow in coronary artery vascular smooth muscle cell proliferation, migration and disease. Unfortunately, the initial success rates after an- accumulation of extracellular matrix (ECM), processes implicated in the development of restenosis [3–5]. Insulin- like growth factor-I (IGF-1) is one of the most potent * smooth muscle cell mitogens known [6]. Transforming Corresponding author. Tel.: 1 1-352-846-2236; fax: 1 1-352-846- 2231; e-mail: gregocc@medicine.ufl.edu growth factor-b (TGF-b) is expressed by smooth muscle 0167-0115 / 99 / $ – see front matter  1999 Elsevier Science B.V. All rights reserved. PII: S0167-0115(98)00027-5