Is interleukin-1 beta a triggering factor for restenosis?
Authors: B Oemar
Journal: Cardiovascular Research (1999)

See article by Chamberlain et al. [9] ( pages 156 -165) inthree different waves [2,12].The first wave is characterthis issue.ized by replication of vascular smooth muscle cells (VSMCs) within the tunica media during the first 2 days Today, more than 20 years after percutaneous translumi-after injury.Several lines of evidence suggest that basic nal coronary angioplasty (PTCA) was introduced into the fibroblast growth factor (bFGF) plays an important role in clinic by Andreas Gruntzig [1], PTCA has become a mediating this first wave of medial smooth muscle proliferwell-established and routine procedure for myocardial ation [13].The second wave (day 2-14) of the response to revascularization of patients with coronary heart disease injury involves the migration of VSMCs from the tunica (CHD).However, restenosis occurs in these patients at a media into the intima.PDGF appears to play an important rate between 30 and 50%, despite a successful initial role as a chemoattractant for VSMCs in this phase [14,15].procedure (for an extensive reviews see Refs.[2][3][4][5]).MoreThe third wave is characterized by intimal VSMC proliferthan 60 large-scale clinical trials later, we are still struggl-ation and accumulation of extracellular matrix, where both ing to understand why restenosis occurs in some but not in PDGF and bFGF continue to provide the stimulus for cell others, and why after 20 years the rate of restenosis is replication.In addition, TGF-b plays an important role in virtually unchanged, despite the availability of modern stimulating the VSMCs to produce excess extracellular therapeutics and extensive knowledge in vascular biology matrix [16].[6][7][8].The paper presented in this issue [9] intriguingly Where does IL-1b fit into these processes?Overwhelmputs interleukin-1b (IL-1b) onto center stage as a possible ing evidence suggests that IL-1b is present and may play a triggering factor in the initiation process of restenosis, and role in different stages of experimental 'restenosis' in may provide us with a handle for successful therapeutic animal models, as well as in human atherosclerosis and intervention.restenosis.However, it is not yet clear where IL-1b is According to current concepts, three processes (phases) located in the cascade of events leading to restenosis after have been postulated to lead to post PTCA restenosis in the injury.Chamberlain et al. [9] provide strong evidence patients [10].Phase I is the acute lumen loss which occurs that IL-1b along with Caspase-1 (also known as in some patients, and is termed elastic 'recoil'.Recoil interleukin-1b converting enzyme, ICE) expression are develops within hours of the intervention and appears to be induced in porcine coronary arteries as early as 1 h after the consequence of overstretching.Phase II is the mural balloon injury.Caspase-1 cleaves pro-IL-1b to generate thrombus formation which results from endothelium re-mature IL-1b, and is necessary for IL-1b activation.IL-1b moval, and the exposure of deep vascular structures and was found not only in inflammatory cells, but more induction of procoagulant factors.These thrombi are rich importantly in endothelial cells and adventitial fibroblasts.in cytokines and growth factors, including interleukin-1b, What are the implications of these findings?platelet-derived growth factor (PDGF), and transforming IL-1b is a pro-inflammatory cytokine with pleiotropic growth factor-b (TGF-b) [11].Finally, phase III is marked effects implicated in the development of atherosclerosis by smooth muscle cell activation and synthesis of extracel- [17].It is produced primarily in activated macrophages; lular matrix.Phase III is considered to be crucial in the however, a number of cell types including endothelial development of late lumen loss and can be divided into cells, VSMCs, and fibroblasts have been shown to produce .Several lines of evidence suggest that IL-1b actively participates in regulating vascular cell functions