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Current Cardiology Reviews


ISSN (Print): 1573-403X
ISSN (Online): 1875-6557

General Review Article

Platelets in In-stent Restenosis: From Fundamental Role to Possible Prognostic Application

Author(s): Habib Haybar, Seyed M.S. Pezeshki and Najmaldin Saki*

Volume 16 , Issue 4 , 2020

Page: [285 - 291] Pages: 7

DOI: 10.2174/1573403X15666190620141129

Price: $65


Background: Introduction of new generations of stents has decreased the percentage of patients experiencing in-stent restenosis (ISR) following the implantation of stent. However, a large number of patients are still afflicted with this phenomenon, which necessitates further study of ISR pathophysiology.

Methods: Relevant English literature was searched up to 2018 and retrieved form the PubMed database and Google Scholar search engine. The following keywords were used: "In-stent restenosis", "Platelet", "Chemokine", "Inflammation", "Vascular smooth muscle cell" and "Neointima".

Results: Previous studies have shown that ISR is a pathophysiologic response to damage of the artery wall after its elongation and separation of the atherosclerotic plaque. Development of neointimal hyperplasia (NIH) following this pathophysiologic response is a function of inflammation caused by platelets, monocytes, macrophages, and lymphocytes, as well as rapid migration and proliferation of generally quiescent cells in the median layer of the artery wall.

Conclusion: After damage to the artery wall, platelets play an essential role in the incidence of NIH by contributing to inflammation and migration of vascular smooth muscle cells and extracellular matrix remodeling, especially via secretion of different chemokines; therefore, developing therapeutic strategies for platelet inhibition in a controlled manner could be the basis of preventive treatments in the near future. In this study, for the first time, we hypothesize that evaluation of platelet activity profile in patients before and after stent implantation may determine the prognosis and likelihood of ISR.

Keywords: In-stent restenosis, platelet, chemokine, inflammation, vascular smooth muscle cell, neointima.

Graphical Abstract
Byrne RA, Joner M, Kastrati A. Stent thrombosis and restenosis: What have we learned and where are we going? The Andreas Grüntzig Lecture ESC 2014. Eur Heart J 2015; 36(47): 3320-31.
[] [PMID: 26417060]
Dangas GD, Claessen BE, Caixeta A, Sanidas EA, Mintz GS, Mehran R. In-stent restenosis in the drug-eluting stent era. J Am Coll Cardiol 2010; 56(23): 1897-907.
[] [PMID: 21109112]
Byrne RA. Restenosis after drug-eluting stenting–a call for action. The New Benchmark for DES 2017; p. 103.
Cassese S, Byrne RA, Tada T, et al. Incidence and predictors of restenosis after coronary stenting in 10 004 patients with surveillance angiography. Heart 2014; 100(2): 153-9.
[] [PMID: 24270744]
Mansour OY, Ibrahim A, Talaat M. Restenosis predictors after carotid angioplasty and stenting and its influence on procedure durability, single-center experience. J Stroke Cerebrovasc Dis 2017; 26(10): 2215-22.
[] [PMID: 28688714]
Li TD, Zeng ZH. Adiponectin as a potential therapeutic target for the treatment of restenosis. Biomed Pharmacother 2018; 101: 798-804.
[] [PMID: 29525676]
Mitra AK, Agrawal DK. In stent restenosis: Bane of the stent era. J Clin Pathol 2006; 59(3): 232-9.
[] [PMID: 16505271]
Ando H, Suzuki A, Sakurai S, et al. Tissue characteristics of neointima in late restenosis: Integrated backscatter intravascular ultrasound analysis for in-stent restenosis. Heart Vessels 2017; 32(5): 531-8.
[] [PMID: 27730297]
Elmore JB, Mehanna E, Parikh SA, Zidar DA. Restenosis of the coronary arteries. coronary and endovascular stents, An issue of interventional cardiology clinics. E-Book 2016; 5(3): 281.
Gasser TC, Ogden RW, Holzapfel GA. Hyperelastic modelling of arterial layers with distributed collagen fibre orientations. J R Soc Interface 2006; 3(6): 15-35.
[] [PMID: 16849214]
Libby P, Hansson GK. Inflammation and immunity in diseases of the arterial tree: Players and layers. Circ Res 2015; 116(2): 307-11.
[] [PMID: 25593275]
Haybar H, Shahrabi S, Rezaeeyan H, Shirzad R, Saki N. Endothelial cells: From dysfunction mechanism to pharmacological effect in cardiovascular disease. Cardiovasc Toxicol 2019; 19(1): 13-22.
[PMID: 30506414]
Dilley RJ, McGeachie JK, Prendergast FJ. A review of the histologic changes in vein-to-artery grafts, with particular reference to intimal hyperplasia. Arch Surg 1988; 123(6): 691-6.
[] [PMID: 3285807]
Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med 1999; 340(2): 115-26.
[] [PMID: 9887164]
Newby AC, Zaltsman AB. Molecular mechanisms in intimal hyperplasia. J Pathol 2000; 190(3): 300-9.
[<300:AID-PATH596>3.0.CO;2-I] [PMID: 10685064]
Golebiewska EM, Poole AW. Platelet secretion: From haemostasis to wound healing and beyond. Blood Rev 2015; 29(3): 153-62.
[] [PMID: 25468720]
Gleissner CA, von Hundelshausen P, Ley K. Platelet chemokines in vascular disease. Arterioscler Thromb Vasc Biol 2008; 28(11): 1920-7.
[] [PMID: 18723831]
Gremmel T, Frelinger AL III, Michelson AD, Eds. Platelet physiology seminars in thrombosis and hemostasis. Thieme Medical Publishers 2016.
Bennett MR, O’Sullivan M. Mechanisms of angioplasty and stent restenosis: Implications for design of rational therapy. Pharmacol Ther 2001; 91(2): 149-66.
[] [PMID: 11728607]
Costa MA, Simon DI. Molecular basis of restenosis and drug-eluting stents. Circulation 2005; 111(17): 2257-73.
[] [PMID: 15867193]
Welt FG, Rogers C. Inflammation and restenosis in the stent era. Arterioscler Thromb Vasc Biol 2002; 22(11): 1769-76.
[] [PMID: 12426203]
Webb LM, Ehrengruber MU, Clark-Lewis I, Baggiolini M, Rot A. Binding to heparan sulfate or heparin enhances neutrophil responses to interleukin 8. Proc Natl Acad Sci USA 1993; 90(15): 7158-62.
[] [PMID: 8346230]
Rollins BJ. Monocyte chemoattractant protein 1: A potential regulator of monocyte recruitment in inflammatory disease. Mol Med Today 1996; 2(5): 198-204.
[] [PMID: 8796888]
Horvath C, Welt FG, Nedelman M, Rao P, Rogers C. Targeting CCR2 or CD18 inhibits experimental in-stent restenosis in primates: inhibitory potential depends on type of injury and leukocytes targeted. Circ Res 2002; 90(4): 488-94.
[] [PMID: 11884380]
Chistiakov DA, Orekhov AN, Bobryshev YV. Vascular smooth muscle cell in atherosclerosis. Acta Physiol (Oxf) 2015; 214(1): 33-50.
[] [PMID: 25677529]
Alfonso F, Byrne RA, Rivero F, Kastrati A. Current treatment of in-stent restenosis. J Am Coll Cardiol 2014; 63(24): 2659-73.
[] [PMID: 24632282]
Graff J, Klinkhardt U, Schini-Kerth VB, et al. Close relationship between the platelet activation marker CD62 and the granular release of platelet-derived growth factor. J Pharmacol Exp Ther 2002; 300(3): 952-7.
[] [PMID: 11861803]
Schmidt R, Bültmann A, Fischel S, et al. Extracellular matrix metalloproteinase inducer (CD147) is a novel receptor on platelets, activates platelets, and augments nuclear factor kappaB-dependent inflammation in monocytes. Circ Res 2008; 102(3): 302-9.
[] [PMID: 18048771]
Bacon K, Baggiolini M, Broxmeyer H, et al. Chemokine/chemokine receptor nomenclature. J Interferon Cytokine Res 2002; 22(10): 1067-8.
[] [PMID: 12433287]
McFadyen JD, Kaplan ZS. Platelets are not just for clots. Transfus Med Rev 2015; 29(2): 110-9.
[] [PMID: 25680870]
Haybar H, Shahrabi S, Deris Zayeri Z, Pezeshki S. Strategies to increase cardioprotection through cardioprotective chemokines in chemotherapy-induced cardiotoxicity. Int J Cardiol 2018; 269: 276-82.
[] [PMID: 30054148]
Weber C. Platelets and chemokines in atherosclerosis: Partners in crime. Circ Res 2005; 96(6): 612-6.
[] [PMID: 15802619]
Balabanian K, Lagane B, Infantino S, et al. The chemokine SDF-1/CXCL12 binds to and signals through the orphan receptor RDC1 in T lymphocytes. J Biol Chem 2005; 280(42): 35760-6.
[] [PMID: 16107333]
Indolfi C, Mongiardo A, Curcio A, Torella D. Molecular mechanisms of in-stent restenosis and approach to therapy with eluting stents. Trends Cardiovasc Med 2003; 13(4): 142-8.
[] [PMID: 12732447]
Charles R, Sandirasegarane L, Yun J, et al. Ceramide-coated balloon catheters limit neointimal hyperplasia after stretch injury in carotid arteries. Circ Res 2000; 87(4): 282-8.
[] [PMID: 10948061]
Pollman MJ, Hall JL, Gibbons GH. Determinants of vascular smooth muscle cell apoptosis after balloon angioplasty injury. Influence of redox state and cell phenotype. Circ Res 1999; 84(1): 113-21.
[] [PMID: 9915780]
Pyles JM, March KL, Franklin M, Mehdi K, Wilensky RL, Adam LP. Activation of MAP kinase in vivo follows balloon overstretch injury of porcine coronary and carotid arteries. Circ Res 1997; 81(6): 904-10.
[] [PMID: 9400370]
Cospedal R, Lobo M, Zachary I. Differential regulation of extracellular signal-regulated protein kinases (ERKs) 1 and 2 by cAMP and dissociation of ERK inhibition from anti-mitogenic effects in rabbit vascular smooth muscle cells. Biochem J 1999; 342(Pt 2): 407-14.
[] [PMID: 10455028]
Jeremy JY, Rowe D, Emsley AM, Newby AC. Nitric oxide and the proliferation of vascular smooth muscle cells. Cardiovasc Res 1999; 43(3): 580-94.
[] [PMID: 10690330]
Wang Y, Kovanen PT. Heparin proteoglycans released from rat serosal mast cells inhibit proliferation of rat aortic smooth muscle cells in culture. Circ Res 1999; 84(1): 74-83.
[] [PMID: 9915776]
Fattori R, Piva T. Drug-eluting stents in vascular intervention. Lancet 2003; 361(9353): 247-9.
[] [PMID: 12547552]
Campo G, Tebaldi M, Vranckx P, et al. Short- versus long-term duration of dual antiplatelet therapy in patients treated for in-stent restenosis: A PRODIGY trial substudy (Prolonging Dual Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia). J Am Coll Cardiol 2014; 63(6): 506-12.
[] [PMID: 24161321]
Song PS, Song YB, Yang JH, et al. Triple vs. dual antiplatelet therapy after percutaneous coronary intervention for coronary bifurcation lesions: Results from the COBIS (COronary BIfurcation Stent) II Registry. Heart Vessels 2015; 30(4): 458-68.
[] [PMID: 24682436]
Lee HJ, Yu CW, Hwang HK, et al. Long-term effectiveness and safety of triple versus dual antiplatelet therapy after percutaneous coronary intervention for unprotected left main coronary artery disease. Coron Artery Dis 2013; 24(7): 542-8.
[] [PMID: 23994880]
Youn YJ, Lee JW, Ahn SG, et al. Multicenter randomized trial of 3-month cilostazol use in addition to dual antiplatelet therapy after biolimus-eluting stent implantation for long or multivessel coronary artery disease. Am Heart J 2014; 167(2): 241-248.e1.
[] [PMID: 24439986]
Han Y, Li Y, Wang S, et al. Cilostazol in addition to aspirin and clopidogrel improves long-term outcomes after percutaneous coronary intervention in patients with acute coronary syndromes: A randomized, controlled study. Am Heart J 2009; 157(4): 733-9.
[] [PMID: 19332203]
Zhao S, Zhong Z, Qi G, Shi L, Tian W. Effects of cilostazol-based triple antiplatelet therapy versus dual antiplatelet therapy after coronary drug-eluting stent implantation: An updated meta-analysis of the randomized controlled trials. Clin Drug Investig 2019; 39(1): 1-13.
[] [PMID: 30251232]
Kim HK, Jeong MH, Lim KS, et al. Effects of ticagrelor on neointimal hyperplasia and endothelial function, compared with clopidogrel and prasugrel, in a porcine coronary stent restenosis model. Int J Cardiol 2017; 240: 326-31.
[] [PMID: 28487152]
Bonello L, Frere C, Cointe S, et al. Ticagrelor increases endothelial progenitor cell level compared to clopidogrel in acute coronary syndromes: A prospective randomized study. Int J Cardiol 2015; 187: 502-7.
[] [PMID: 25846661]
Li P, Yang Y, Chen T, et al. Ticagrelor overcomes high platelet reactivity in patients with acute myocardial infarction or coronary artery in-stent restenosis: A randomized controlled trial. Sci Rep 2015; 5: 13789.
[] [PMID: 26350388]
Kunicki TJ, Williams SA, Nugent DJ. Genetic variants that affect platelet function. Curr Opin Hematol 2012; 19(5): 371-9.
[] [PMID: 22872156]
Feher G, Feher A, Pusch G, Lupkovics G, Szapary L, Papp E. The genetics of antiplatelet drug resistance. Clin Genet 2009; 75(1): 1-18.
[] [PMID: 19067731]
Lin YJ, Li JW, Zhang MJ, et al. The association between CYP2C19 genotype and of in-stent restenosis among patients with vertebral artery stent treatment. CNS Neurosci Ther 2014; 20(2): 125-30.
[] [PMID: 24330577]
Sibbing D, Koch W, Gebhard D, et al. Cytochrome 2C19*17 allelic variant, platelet aggregation, bleeding events, and stent thrombosis in clopidogrel-treated patients with coronary stent placement. Circulation 2010; 121(4): 512-8.
[] [PMID: 20083681]
Guo B, Tan Q, Guo D, Shi Z, Zhang C, Guo W. Patients carrying CYP2C19 loss of function alleles have a reduced response to clopidogrel therapy and a greater risk of in-stent restenosis after endovascular treatment of lower extremity peripheral arterial disease. J Vasc Surg 2014; 60(4): 993-1001.
[] [PMID: 24877854]
Chen W, Huang F, Li M, Jiang Y, He J, Li H, et al. Incidence and predictors of the in-stent restenosis after vertebral artery ostium stenting. J Stroke Cerebrovasc Dis 2018; 27(11): 3030-5.
Byrne RA, Joner M, Kastrati A. Stent thrombosis and restenosis: What have we learned and where are we going? The Andreas Grüntzig Lecture ESC 2014. Eur Heart J 2015; 36(47): 3320-31.
[] [PMID: 26417060]
Tornyos A, Aradi D, Horváth IG, et al. Clinical outcomes in patients treated for coronary in-stent restenosis with drug-eluting balloons: Impact of high platelet reactivity. PLoS One 2017; 12(12)e0188493
[] [PMID: 29216314]
Johansen O, Brekke M, Seljeflot I, Semb AG, Arnesen H. Blood platelet count and reactivity are associated with restenosis 6 months after coronary angioplasty. Scand Cardiovasc J 2004; 38(4): 211-5.
[] [PMID: 15553931]
Dai Z, Gao J, Li S, et al. mean platelet volume as a predictor for restenosis after carotid angioplasty and stenting. Stroke 2018; 49(4): 872-6.
[] [PMID: 29559579]
Santulli G, Wronska A, Uryu K, et al. A selective microRNA-based strategy inhibits restenosis while preserving endothelial function. J Clin Invest 2014; 124(9): 4102-14.
[] [PMID: 25133430]
Kornowski R, Hong MK, Tio FO, Bramwell O, Wu H, Leon MB. In-stent restenosis: Contributions of inflammatory responses and arterial injury to neointimal hyperplasia. J Am Coll Cardiol 1998; 31(1): 224-30.

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