E-Selectin and restenosis after femoropopliteal angioplasty: prognostic impact of the Ser128Arg genotype and plasma levels

Summary

Perivascular inflammation plays a key role in the development of restenosis after percutaneous transluminal angioplasty (PTA).The adherence of leucocytes to the activated endothelium, an essential feature in the restenotic process, is mediated by the cellular adhesion molecule E-Selectin. A DNA polymorphism in the regulator region of E-Selectin at codon 561 (Ser128Arg) is suggested to modulate the molecule’s physiological effects. Therefore, we investigated the association between the E-Selectin Ser128Arg genotype, E-Selectin plasma levels and restenosis after femoropopliteal PTA. We prospectively studied 175 consecutive patients with peripheral artery disease and intermittent claudication (n=126) or critical limb ischemia (n=49) who underwent primary successful femoropopliteal balloon angioplasty. E-Selectin Ser128Arg genotype and baseline E-Selectin plasma levels were determined and patients were followed up for median 12 months (IQR 11 to 14, total range 6 to 24) for the occurrence of postangioplasty restenosis (≥50%). E-Selectin plasma levels in homozygous Arg128Arg and heterozygous Ser128Arg patients were significantly higher compared to wildtype Ser128Ser patients (p=0.041). Patency rates for wildtype Ser128Ser, heterozygous Ser128Arg and homozygous Ser128Ser patients were 57%, 44% and 50% at 6 months, and 46%, 40% and 17%, at 12 months, respectively (Log Rank p=0.31). Patency rates for increasing tertiles of E-Selectin were 61%, 58% and 37% at 6 months, and 54%, 45% and 30% at 12 months, respectively (Log Rank p=0.020). Patients with an E-Selectin plasma level above 44.9 mg/dL (third tertile) had an 1.9-fold increased adjusted risk for restenosis (95% CI 1.09 to 3.30). E-Selectin plasma levels are modulated by the E-Selectin Ser128Arg genotype, and predict the risk for restenosis after PTA in patients with PAD. A direct association of the Ser128Arg polymorphism with late postangioplasty failure could not be demonstrated.

Keywords

Angioplasty - restenosis - genes - polymorphism - E-Selectin

• References

• 1 TransAtlantic Inter-Society Consensus (TASC). Management of peripheral arterial disease (PAD). Eur J Vasc Endovasc Surg 2000; 19: S1-S250.
• 2 Varty K, Bolia A, Naylor AR. et al. Infrapopliteal percutaneous transluminal angioplasty: a safe and successful procedure. Eur J Vasc Surg 1995; 09: 341-5.
• 3 Morgenstern BR, Getraidmann GJ, Laffey KJ. et al. Total occlusions of the femoropopliteal artery: high technical success rate of conventional balloon angioplasty. Radiology 1989; 172: 937-40.
• 4 Tsakiris DA, Tschöpl M, Jaeger K. et al. Circulating cell adhesion molecules and endothelial markers before and after transluminal angioplasty in peripheral arterial occlusive disease. Atherosclerosis 1999; 142: 193-200.
• 5 Waller BF, Pingkerton CA, Orr CM. et al. Morphological observations late (>30°) after clinically successful coronary balloon angioplasty in the atherosclerotic rabbit. Circulation 1991; 83: 28-41.
• 6 Belch JJF, Shaw JW, Kirk G. et al. The white blood cell adhesion molecule E-Selectin predicts restenosis in patients with intermittent claudication undergoing percutaneous transluminal angioplasty. Circulation 1997; 95: 2027-31.
• 7 McBride W, Lange RA, Hillis DL. Restenosis after successful coronary angioplasty: pathophysiology and prevention. N Engl J Med 1988; 318: 1734-7.
• 8 Frenette PS, Wagner DD. Adhesion molecules, I. N Engl J Med 1996; 334: 1526-9.
• 9 Frenette PS, Wagner DD. Adhesion molecules, II. N Engl J Med 1996; 335: 43-5.
• 10 Barron MK, Scott RLake, Buda AJ. et al. Intimal hyperplasia after balloon injury is attenuated by blocking selectins. Circulation 1997; 96: 3587-92.
• 11 Inoue T, Hoshi K, Yaguchi I. et al. Serum levels of circulating adhesion molecules after coronary angioplasty. Cardiology 1999; 91: 236-42.
• 12 Wenzel K, Felix S, Kleber FX. et al. ESelectin polymorphism and atherosclerosis: an association study. Hum Mol Genet 1994; 03: 1935-7.
• 13 Wenzel K, Ernst M, Rohde K. et al. DANN polymorphism in adhesion molecule genes – a new risk factor for early atherosclerosis. Hum Genet 1996; 97: 15-20.
• 14 Rauchhaus M, Gross M, Schulz S. et al. The E-Selectin SER128ARG gene polymorphism and restenosis after successful coronary angioplasty. Int J Card 2002; 83: 249-57.
• 15 Bevilacqua MP, Stengelin S, Gimbrone MAJ. et al. Endothelial leucocyte adhesion molecule 1: an inducible receptor for neutrophils related to complement regulatory proteins and lectins. Science 1989; 243: 1160-5.
• 16 Schillinger M, Exner M, Mlekusch W. et al. Balloon angioplasty and stentimplantation induce a vascular inflammatory reaction. J Endovasc Ther 2002; 09: 59-66.
• 17 Schillinger M, Exner M, Mlekusch W. et al. Vascular inflammation and percutaneous transluminal angioplasty of the femoropopliteal artery: Association with restenosis. Radiology 2002; 225: 21-6.
• 18 Schillinger M, Exner M, Mlekusch W. et al. Fibrinogen predicts restenosis after endovascular treatment of the iliac arteries. Thromb Haemost 2002; 87: 959-65.
• 19 Ridker PM, Cushman M, Stampfer MJ. et al. Plasma concentration of C-reactive protein and Risk of Developing peripheral vascular disease. Circulation 1998; 97: 425-8.
• 20 Ranke C, Creutzig A, Alexander K. Duplex scanning of the peripheral arteries: correlation of the peak velocity ratio with angiographic diameter reduction. Ultrasound Med Biol 1992; 18: 433-40.
• 21 Rust S, Funke H, Assmann G. Mutagenically separated PCR (MS-PCR): a highly specific one step procedure for easy mutation detection. Nucleic Acids Res 1993; 21: 3623-9.
• 22 Ferri C, Desideri G, Baldoncini R. et al. Early activation of vascular endothelium in non-obese, nondiabetic essential hypertensive patients with multiple metabolic abnormalities. Diabetes 1998; 47: 660-7.
• 23 Ellsworth DL, Bielack LF, Turner ST. et al. Gender- and age-dependent relationship between the E-Selectin S128R polymorphism and coronary artery calcification. J Mol Med 2001; 79: 390-8.
• 24 Caulin-Glaser T, Farrel WJ, Pfau SE. et al. Modulation of circulating cellular adhesion molecules in postmenopausal women with coronary artery disease. J Am Coll Cardiol 1998; 31: 1555-60.
• 25 Gordon DJ, Castelli WP, Hjortland MC. et al. High density lipoprotein as a protective factor against coronary heart disease. the Framingham study. Am J Med 1977; 62: 707-14.
• 26 Stannard AK, Khan S, Graham A. et al. Inability of plasma high-density lipoproteins to inhibit cell adhesion molecule expression in human coronary artery endothelial cells. Atherosclerosis 2001; 154: 31-8.
• 27 Cockerill GW, Rye KA, Gamble JR. et al. High-density lipoproteins inhibit cytocineinduced expression of endothelial cell adhesion molecules. Arterioscler Thromb Vasc Biol 1995; 15: 1987-94.
• 28 Tsakiris DA, Tschöpl M, Jäger K. et al. Circulating cell adhesion molecules and endothelial markers before and after transluminal angioplasty in peripheral arterial occlusive disease. Atherosclerosis 1999; 142: 193-200.
• 29 Bannan S, Mansfield MW, Grant PJ. Soluble vascular cell adhesion molecules-1 and E- Selectin levels in relation to vascular risk factors and to E-Selectin genotype in the first degree relatives of NIDDM patients and in NIDDM patients. Diabetologia 1998; 41: 4606.
• 30 Ray KK, Camp NJ, Bennett CE. et al. Genetic variation at the interlaukin-1 locus is a determinant of changes in soluble endothelial factors in patients with acute coronary syndromes. Clin Science 2002; 103: 303-10.
• 31 Bauters C, Lamblin N, Amouyel P. Gene polymorphisms and outcome after coronary angioplasty. Curr Interv Cardiol Rep 2001; 03: 281-6.
• 32 Exner M, Schillinger M, Minar E. et al. Heme oxygenase-1 gene promoter microsatellite polymorphism is associated with restenosis after percutaneous transluminal angioplasty. J Endovasc Ther 2001; 08: 433-40.
• 33 Johnston KW. Femoral and popliteal arteries: reanalysis of results of balloon angioplasty. Radiology 1992; 183: 767-71.
• 34 Schillinger M, Mlekusch W, Haumer M. et al. Angioplasty and elective stenting of de novo versus recurrent femoropopliteal lesions: 1-year follow-up. J Endovasc Ther 2003; 10: 288-97.