Schillinger and Minar injury or stent implantation initiates hypertrophic neointima formation through vascular smooth muscle cell (VSMC) proliferation and constrictive vascular remodelling (O’Brian and Schwartz 1994; Ross 1999; Orford et al 2000). This process of neointima formation and recurrent lumen narrowing has been referred to as manifestation of an inflammatory wound healing response expressed specifically in vascular tissue (Forrester et al 1991). The present article reviews recent findings on the issue of inflammation and restenosis with special attention to the peripheral vessel area. Pathophysiology of inflammation and restenosis Chronic vascular inflammation is involved in the development of restenosis after balloon angioplasty and stent implantation (Forrester et al 1991; Belch et al 1997; Serrano et al 1997; Kamijikkoku et al 1998; Kornowski et al 1998; Tsakiris et al 1999; Yutani et al 1999; Lusis 2000; Cippolone et al 2001; Glass and Witztum 2001; Schillinger et al 2001, 2002a; Libby et al 2002). Broadly, restenosis can be considered to be a form of hypertrophic wound healing resulting from an interaction between monocyte-derived macrophages, T cells, and the normal cellular elements of the arterial wall. A triggering event for the vascular inflammatory process is shear stress during balloon inflation or stent implantation and vascular injury, which stimulate the production of proinflammatory molecules and activation of circulating monocytes (Serrano et al 1997). Expression of selectins and adhesion molecules mediate the binding of circulating monocytes and penetration of these cells into the vascular wall (Ross 1999; Lusis 2000; Glass and Witztum 2001; Libby et al 2002). The magnitude of monocyte activation and adherence to the vascular wall was suggested to promote late lumen loss (Pietersma et al 1995; Mickelson et al 1996). The first step in adhesion of inflammatory cells at the dilated or stented segment, the “rolling” of leucocytes, is mediated by selectins, which bind to carbohydrate ligands on leukocytes. The E-selectin serum level, for example, has been demonstrated to closely correlate with the restenosis risk (Belch et al 1997). The firm adhesion of monocytes and T cells to the arterial wall is then mediated via cell adhesion molecules (CAMs); CAMs have also been shown to be associated with the restenotic process (Kamijikkoku et al 1998; Tsakiris et al 1999). Once adherent to the endothelium, the monocytes penetrate into the intima and through the media to the adventitia (Wilcox et al 2001). Monocyte chemotactic protein-1 (MCP 1) appears responsible for monocyte recruitment and direct transmigration into the vascular wall at the treated lesion, and higher serum levels of this chemokine indicate a higher restenosis risk (Cipollone et al 2001). Once resident in the arterial wall, the blood-derived inflammatory cells participate in and perpetuate a local inflammatory response. Inflammatory molecules as well as shear stress during the endovascular procedure stimulate the immigration of VSMCs from the medial layer of the arterial wall past the internal elastic lamina and into the intimal or subendothelial space. Recruitment and proliferation of myofibroblasts and synthesis of extracellular matrix proteins are key factors of hypertrophic neointima formation and restenosis (Wilcox et al 2001). This phase of lesion progression is markedly influenced by interactions between monocyte/macrophages and T cells, which results in the acquisition of many features of a chronic inflammatory state. Predictive value of inflammatory markers and acute phase proteins Acute phase reactants are related to atherosclerosis in the peripheral, coronary, and extracranial brain arteries (Heinrich et al 1995; Tschöpl et al 1997; Blum et al 1998; Buffon et al 1999; Schillinger et al 2002b, 2003a, 2003b). These circulating markers of inflammation reflect the activity of the disease associated with accumulation of macrophages and proliferation of endothelial cells and vascular smooth muscle cells (Haverkate et al 1997). The plasma proteins, C-reactive protein (CRP), serum amyloid A (SAA), and fibrinogen are sensitive, specific, and fast reacting markers of acute phase reaction (Pepys and Baltz 1983; Young et al 1991; Ernst 1993) and provide an indirect measure of a cytokine dependent inflammatory process of the arterial wall (Pepys 1995; Kuller et al 1996). Balloon injury and stent implantation in the peripheral vessel area have been demonstrated to induce a vascular inflammatory response at the dilated vessel segment, which is measurable by the postintervention course of serum acute phase parameters like CRP, SAA, or fibrinogen (Schillinger et al 2002c), and the severity of arterial injury during balloon injury or stent placement correlated with increased inflammation (Virmani and Farb 1999). It is well known that patency rates after percutaneous transluminal angioplasty and stent implantation widely depend on the location of the treated lesion. Endovascular treatment of large elastic arteries like the internal carotid 74 Vascular Health and Risk Management 2005:1(1)