Vitronectin and Urokinase-Type Plasminogen Activator Gene Expression Levels Are Increased in Patients with Coronary Artery In-Stent Restenosis

Abstract

Neointimal hyperplasia is known as a main factor contributing to in-stent restenosis (ISR). Monocytes may play a central role in vessel restenosis process after stent implantation. The aim of this study was to investigate the relationships between the urokinase-type plasminogen activator (PLAU) and vitronectin (Vtn) gene expression levels in peripheral blood mononuclear cell samples isolated from whole blood of 66 patients undergoing coronary artery angiography (22 controls, stenosis < 0.05%; 22 with stent no-restenosis and stenosis < 70%; and 22 with ISR and stenosis > 70%). The Vtn and PLAU gene expression levels were measured by real-time quantitative polymerase chain reaction technique. The age- and gender-independent increases in the expression levels of Vtn (17-fold; p < 0.001) and PLAU (27-fold; p < 0.0001) genes were found in the patients with ISR as compared with the control group. The results suggested that the Vtn and PLAU genes may be involved in the coronary artery ISR.

Keywords

in-stent restenosis - vitronectin - urokinase-type plasminogen activator

• References

• 1 Yang ZK, Shen Y, Hu J. , et al. Impact of coronary collateral circulation on angiographic in-stent restenosis in patients with stable coronary artery disease and chronic total occlusion. Int J Cardiol 2017; 227: 485-489
• 2 Fischman DL, Leon MB, Baim DS. , et al; Stent Restenosis Study Investigators. A randomized comparison of coronary-stent placement and balloon angioplasty in the treatment of coronary artery disease. N Engl J Med 1994; 331 (08) 496-501
• 3 Indolfi C, Pavia M, Angelillo IF. Drug-eluting stents versus bare metal stents in percutaneous coronary interventions (a meta-analysis). Am J Cardiol 2005; 95 (10) 1146-1152
• 4 Denes L, Entz L, Jancsik V. Restenosis and therapy. Int J Vasc Med 2012; 2012: 406236
• 5 Serruys PW, de Jaegere P, Kiemeneij F. , et al; Benestent Study Group. A comparison of balloon-expandable-stent implantation with balloon angioplasty in patients with coronary artery disease. N Engl J Med 1994; 331 (08) 489-495
• 6 Hoffmann R, Mintz GS. Coronary in-stent restenosis - predictors, treatment and prevention. Eur Heart J 2000; 21 (21) 1739-1749
• 7 Hong YJ, Jeong MH, Ahn Y. , et al. Incidence, predictors, and clinical impact of tissue prolapse after stent implantation for saphenous vein graft disease: intravascular ultrasound study. Int J Cardiol 2013; 168 (03) 3073-3075
• 8 Thorpe PE. Identification and treatment of restenosis in failing venous stents: the role of intravascular ultrasound. J Vasc Surg Venous Lymphat Disord 2014; 2 (01) 109-110
• 9 Wang YL, Liu LZ, He ZH, Ding KH, Xue F. Phenotypic transformation and migration of adventitial cells following angioplasty. Exp Ther Med 2012; 4 (01) 26-32
• 10 Baldwin JF, Sood V, Elfline MA. , et al. The role of urokinase plasminogen activator and plasmin activator inhibitor-1 on vein wall remodeling in experimental deep vein thrombosis. J Vasc Surg 2012; 56 (04) 1089-1097
• 11 Schäfer K, Schroeter MR, Dellas C. , et al. Plasminogen activator inhibitor-1 from bone marrow-derived cells suppresses neointimal formation after vascular injury in mice. Arterioscler Thromb Vasc Biol 2006; 26 (06) 1254-1259
• 12 Ge J, Shen C, Liang C, Chen L, Qian J, Chen H. Elevated matrix metalloproteinase expression after stent implantation is associated with restenosis. Int J Cardiol 2006; 112 (01) 85-90
• 13 Noorabad-Ghahroodi F, Abdi S, Zand AH, Najafi M. HGDB: a web retrieving cardiovascular-associated gene data. Int J Cardiol 2017; 232: 117-120
• 14 Schousboe SL, Egelund R, Kirkegaard T, Preissner KT, Rodenburg KW, Andreasen PA. Vitronectin and substitution of a beta-strand 5A lysine residue potentiate activity-neutralization of PA inhibitor-1 by monoclonal antibodies against alpha-helix F. Thromb Haemost 2000; 83 (05) 742-751
• 15 Cao DJ, Guo YL, Colman RW. Urokinase-type plasminogen activator receptor is involved in mediating the apoptotic effect of cleaved high molecular weight kininogen in human endothelial cells. Circ Res 2004; 94 (09) 1227-1234
• 16 Egashira K, Zhao Q, Kataoka C. , et al. Importance of monocyte chemoattractant protein-1 pathway in neointimal hyperplasia after periarterial injury in mice and monkeys. Circ Res 2002; 90 (11) 1167-1172
• 17 Hirose S, Ashikaga T, Hatano Y. , et al. Treatment of in-stent restenosis with excimer laser coronary angioplasty: benefits over scoring balloon angioplasty alone. Lasers Med Sci 2016; 31 (08) 1691-1696
• 18 Fukuda D, Shimada K, Tanaka A, Kawarabayashi T, Yoshiyama M, Yoshikawa J. Circulating monocytes and in-stent neointima after coronary stent implantation. J Am Coll Cardiol 2004; 43 (01) 18-23
• 19 Moreno PR, Bernardi VH, López-Cuéllar J. , et al. Macrophage infiltration predicts restenosis after coronary intervention in patients with unstable angina. Circulation 1996; 94 (12) 3098-3102
• 20 Khosravi M, Hoseini-Fard SR, Najafi M. System study of vascular smooth muscle cell (VSMC) activation-related signaling pathways by monocyte and macrophage cells. Curr Signal Transduct Ther 2017 12, 10.2174/1574362412666161118173050
• 21 Fuhrman B. The urokinase system in the pathogenesis of atherosclerosis. Atherosclerosis 2012; 222 (01) 8-14
• 22 Linton MF, Babaev VR, Huang J, Linton EF, Tao H, Yancey PG. Macrophage apoptosis and efferocytosis in the pathogenesis of atherosclerosis. Circ J 2016; 80 (11) 2259-2268
• 23 Brown S, Meroueh SO, Fridman R, Mobashery S. Quest for selectivity in inhibition of matrix metalloproteinases. Curr Top Med Chem 2004; 4 (12) 1227-1238
• 24 De Lorenzi V, Sarra Ferraris GM, Madsen JB, Lupia M, Andreasen PA, Sidenius N. Urokinase links plasminogen activation and cell adhesion by cleavage of the RGD motif in vitronectin. EMBO Rep 2016; 17 (07) 982-998
• 25 Hillig T, Engelholm LH, Ingvarsen S. , et al. A composite role of vitronectin and urokinase in the modulation of cell morphology upon expression of the urokinase receptor. J Biol Chem 2008; 283 (22) 15217-15223
• 26 Fleetwood AJ, Achuthan A, Schultz H. , et al. Urokinase plasminogen activator is a central regulator of macrophage three-dimensional invasion, matrix degradation, and adhesion. J Immunol 2014; 192 (08) 3540-3547
• 27 Ekmekçi OB, Ekmekçi H. Vitronectin in atherosclerotic disease. Clin Chim Acta 2006; 368 (1-2): 77-83