Schillinger and Minar measure involves these very factors that are inhibited by HO-1: inflammation in the vessel wall, constrictive vascular remodeling, and hypertrophic neointima formation through smooth muscle cell proliferation. HO-1 is up-regulated by balloon angioplasty. However, humans differ quantitatively in their ability to mount a HO-1 response. There is a length polymorphism in the form of a (GT)n dinucleotide repeat in the 5´-flanking region of the human HO-1 gene that modulates the quantitative level of HO-1 activity in response to a given stimulus (Kimpara et al 1997; Yamada et al 2000). The HO-1 promoter genotype was associated with the postintervention inflammatory response and the occurrence of restenosis after femoropopliteal PTA (Exner et al 2001, Schillinger et al 2002e, 2004). Patients with a certain genotype of the HO-1 gene promoter exhibited a lower postintervention inflammatory response and a lower restenosis rate at 6 months compared with non-carriers of this genetic variant. This suggested that a stronger HO-1 response is protective against restenosis. Modulation of the postintervention vascular inflammatory response seemed to be an underlying mechanism of the protective effect of HO-1 up-regulation after balloon angioplasty. Interleukin 6, on the other hand, represents a key factor in the vascular inflammatory cascade after balloon injury that is directly involved in the regulation of the acute phase response. A functional polymorphism in the IL-6 gene promoter has been demonstrated to modulate the cytokine expression in response to vascular injury (Brull et al 2001). Consistently, this IL-6 promoter polymorphism was associated with the 12 months restenosis risk after femoropopliteal PTA in a larger patient series (Exner et al 2004), indicating a potential involvement of pro- inflammatory genes in the restenotic process. Nevertheless, future research will have to focus on more complex gene–gene and gene–environment interactions, since restenosis likely is a polygenetic process and may not be explained by a single genetic polymorphism. Potential clinical implications Some experimental data indicate that modulation or suppression of the inflammatory response after endovascular treatment may exert beneficial effects on outcome. Statins are known to exert potent antiinflammatory properties and have been demonstrated to reduce inflammation and progression of atherosclerosis. In this context, it has been recently demonstrated that a statin (pitavastatin) has the ability to inhibit neointimal hyperplasia after stenting in a 76 procine coronary model mainly through a reduction of inflammatory reactions (Yokoyama 2004). Furthermore, in patients with persistently high CRP levels after successful coronary artery stent implantation, oral immunosuppressive therapy with prednisone resulted in a striking reduction of clinical events and angiographic restenosis rate (Versaci et al 2002). In contrast to these conventional pharmacological approaches, various gene therapeutic approaches also seemed promising. In hypercholesterolemic rabbits, local adenovirus-mediated I kappa B alpha gene transfer had the potential to reduce intimal hyperplasia after stent placement (Breuss et al 2002; Cejna et al 2002). Similarly, pre- treatment with recombinant antibodies against leukocyte P-selectin glycoprotein ligand-1, a key factor of inflammation and activation of platelets, in a porcine coronary stent model reduced neointimal proliferation and in-stent restenosis (Tanguay et al 2004). Another experimentally successful gene-therapeutic approach to inhibit inflammation and reduce restenosis was the recently described inhibition of early growth response factor 1 in hypercholesterolemic rabbits after carotid balloon injury (Ohtani et al 2004). Conclusion Evidence from experimental, animal, and clinical studies support the hypothesis that vascular inflammation is a key factor in the restenotic process. The extent of vascular inflammation in response to percutaneous angioplasty predicts the restenosis risk, although currently inflammatory markers are not of clinical utility in this context. 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