Pathophysiology of Thrombosis in Peripheral Artery Disease

Author(s): Aida Habib, Giovanna Petrucci, Bianca Rocca*

Journal Name: Current Vascular Pharmacology

Volume 18 , Issue 3 , 2020


Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Abstract:

Under physiological conditions, peripheral arteries release endogenous vascular-protective and antithrombotic agents. Endothelial cells actively synthesize vasoactive mediators, which regulate vascular tone and platelet reactivity thus preventing thrombosis. Atherosclerosis disrupts homeostasis and favours thrombosis by triggering pro-thrombotic responses in the vessels, platelet activation, aggregation as well as vasoconstriction, phenomena that ultimately lead to symptomatic lumen restriction or complete occlusion.

In the present review, we will discuss the homeostatic role of arterial vessels in releasing vascular-protective agents, such as nitric oxide and prostacyclin, the role of pro- and anti-thrombotic vascular receptors as well as the contribution of circulating platelets and coagulation factors in triggering the pro-thrombotic response(s). We will discuss the pathological consequences of disrupting the protective pathways in the arteries and the pharmacological interventions along these pathways.

Keywords: Endothelium, platelets, anti-thrombotic mechanisms, atherothrombosis, EC, VSM.

[1]
Pober JS, Sessa WC. Evolving functions of endothelial cells in inflammation. Nat Rev Immunol 2007; 7(10): 803-15.
[http://dx.doi.org/10.1038/nri2171] [PMID: 17893694]
[2]
Zhao Y, Vanhoutte PM, Leung SW. Vascular nitric oxide: Beyond eNOS. J Pharmacol Sci 2015; 129(2): 83-94.
[http://dx.doi.org/10.1016/j.jphs.2015.09.002] [PMID: 26499181]
[3]
Moncada S, Palmer RM, Higgs EA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 1991; 43(2): 109-42.
[PMID: 1852778]
[4]
Förstermann U, Sessa WC. Nitric oxide synthases: regulation and function. Eur Heart J 2012; 33: 829-37.
[http://dx.doi.org/10.1093/eurheartj/ehr304]
[5]
Bredt DS, Snyder SH. Nitric oxide: a physiologic messenger molecule. Annu Rev Biochem 1994; 63: 175-95.
[http://dx.doi.org/10.1146/annurev.bi.63.070194.001135] [PMID: 7526779]
[6]
Steinert JR, Chernova T, Forsythe ID. Nitric oxide signaling in brain function, dysfunction, and dementia. Neuroscientist 2010; 16(4): 435-52.
[http://dx.doi.org/10.1177/1073858410366481] [PMID: 20817920]
[7]
Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 1980; 288(5789): 373-6.
[http://dx.doi.org/10.1038/288373a0] [PMID: 6253831]
[8]
Minshall RD, Sessa WC, Stan RV, Anderson RG, Malik AB. Caveolin regulation of endothelial function. Am J Physiol Lung Cell Mol Physiol 2003; 285(6): L1179-83.
[http://dx.doi.org/10.1152/ajplung.00242.2003] [PMID: 14604847]
[9]
Kraehling JR, Sessa WC. Contemporary Approaches to modulating the nitric oxide-cGMP pathway in cardiovascular disease. Circ Res 2017; 120(7): 1174-82.
[http://dx.doi.org/10.1161/CIRCRESAHA.117.303776] [PMID: 28360348]
[10]
Mónica FZ, Bian K, Murad F. the endothelium-dependent nitric oxide-cGMP pathway. Adv Pharmacol 2016; 77: 1-27.
[http://dx.doi.org/10.1016/bs.apha.2016.05.001] [PMID: 27451093]
[11]
Moncada S, Higgs EA. The discovery of nitric oxide and its role in vascular biology. Br J Pharmacol 2006; 147(Suppl. 1): S193-201.
[http://dx.doi.org/10.1038/sj.bjp.0706458] [PMID: 16402104]
[12]
Ohta F, Takagi T, Sato H, Ignarro LJ. Low-dose L-arginine administration increases microperfusion of hindlimb muscle without affecting blood pressure in rats. Proc Natl Acad Sci USA 2007; 104(4): 1407-11.
[http://dx.doi.org/10.1073/pnas.0610207104] [PMID: 17229841]
[13]
Shi Y, Vanhoutte PM. Macro- and microvascular endothelial dysfunction in diabetes. J Diabetes 2017; 9(5): 434-49.
[http://dx.doi.org/10.1111/1753-0407.12521] [PMID: 28044409]
[14]
Duplain H, Burcelin R, Sartori C, et al. Insulin resistance, hyperlipidemia, and hypertension in mice lacking endothelial nitric oxide synthase. Circulation 2001; 104(3): 342-5.
[http://dx.doi.org/10.1161/01.CIR.104.3.342] [PMID: 11457755]
[15]
Yatera Y, Shibata K, Furuno Y, et al. Severe dyslipidaemia, atherosclerosis, and sudden cardiac death in mice lacking all NO synthases fed a high-fat diet. Cardiovasc Res 2010; 87(4): 675-82.
[http://dx.doi.org/10.1093/cvr/cvq092] [PMID: 20304785]
[16]
Tsutsui M, Tanimoto A, Tamura M, et al. Significance of nitric oxide synthases: Lessons from triple nitric oxide synthases null mice. J Pharmacol Sci 2015; 127(1): 42-52.
[http://dx.doi.org/10.1016/j.jphs.2014.10.002] [PMID: 25704017]
[17]
Chen JY, Ye ZX, Wang XF, et al. Nitric oxide bioavailability dysfunction involves in atherosclerosis. Biomed Pharmacother 2018; 97: 423-8.
[http://dx.doi.org/10.1016/j.biopha.2017.10.122] [PMID: 29091892]
[18]
Lorin J, Zeller M, Guilland JC, Cottin Y, Vergely C, Rochette L. Arginine and nitric oxide synthase: regulatory mechanisms and cardiovascular aspects. Mol Nutr Food Res 2014; 58(1): 101-16.
[http://dx.doi.org/10.1002/mnfr.201300033] [PMID: 23740826]
[19]
Kashyap VS, Lakin RO, Campos P, et al. The LargPAD Trial: Phase IIA evaluation of l-arginine infusion in patients with peripheral arterial disease. J Vasc Surg 2017; 66(1): 187-94.
[http://dx.doi.org/10.1016/j.jvs.2016.12.127] [PMID: 28366306]
[20]
Reule CA, Goyvaerts B, Schoen C. Effects of an L-arginine-based multi ingredient product on endothelial function in subjects with mild to moderate hypertension and hyperhomocysteinemia - a randomized, double-blind, placebo-controlled, cross-over trial. BMC Complement Altern Med 2017; 17(1): 92.
[http://dx.doi.org/10.1186/s12906-017-1603-9] [PMID: 28153005]
[21]
Long JZ, Li W, Booker L, et al. Selective blockade of 2-arachidonoylglycerol hydrolysis produces cannabinoid behavioral effects. Nat Chem Biol 2009; 5(1): 37-44.
[http://dx.doi.org/10.1038/nchembio.129] [PMID: 19029917]
[22]
Simmons DL, Botting RM, Hla T. Cyclooxygenase isozymes: the biology of prostaglandin synthesis and inhibition. Pharmacol Rev 2004; 56(3): 387-437.
[http://dx.doi.org/10.1124/pr.56.3.3] [PMID: 15317910]
[23]
McAdam BF, Catella-Lawson F, Mardini IA, Kapoor S, Lawson JA, FitzGerald GA. Systemic biosynthesis of prostacyclin by cyclooxygenase (COX)-2: the human pharmacology of a selective inhibitor of COX-2. Proc Natl Acad Sci USA 1999; 96(1): 272-7.
[http://dx.doi.org/10.1073/pnas.96.1.272] [PMID: 9874808]
[24]
Topper JN, Cai J, Falb D, Gimbrone MA Jr. Identification of vascular endothelial genes differentially responsive to fluid mechanical stimuli: cyclooxygenase-2, manganese superoxide dismutase, and endothelial cell nitric oxide synthase are selectively up-regulated by steady laminar shear stress. Proc Natl Acad Sci USA 1996; 93(19): 10417-22.
[http://dx.doi.org/10.1073/pnas.93.19.10417] [PMID: 8816815]
[25]
Bhala N, Emberson J, Merhi A, et al. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet 2013; 382(9894): 769-79.
[http://dx.doi.org/10.1016/S0140-6736(13)60900-9] [PMID: 23726390]
[26]
Grosser T, Ricciotti E, FitzGerald GA. The cardiovascular pharmacology of nonsteroidal anti-inflammatory drugs. Trends Pharmacol Sci 2017; 38(8): 733-48.
[http://dx.doi.org/10.1016/j.tips.2017.05.008] [PMID: 28651847]
[27]
Yu Y, Ricciotti E, Scalia R, et al. Vascular COX-2 modulates blood pressure and thrombosis in mice. Sci Transl Med 2012; 4(132): 132-54.
[http://dx.doi.org/10.1126/scitranslmed.3003787] [PMID: 22553252]
[28]
Cheng Y, Austin SC, Rocca B, et al. Role of prostacyclin in the cardiovascular response to thromboxane A2. Science 2002; 296(5567): 539-41.
[http://dx.doi.org/10.1126/science.1068711] [PMID: 11964481]
[29]
Tang SY, Monslow J, Todd L, Lawson J, Puré E, FitzGerald GA. Cyclooxygenase-2 in endothelial and vascular smooth muscle cells restrains atherogenesis in hyperlipidemic mice. Circulation 2014; 129(17): 1761-9.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.113.007913] [PMID: 24519928]
[30]
Ozen G, Norel X. Prostanoids in the pathophysiology of human coronary artery. Prostaglandins Lipid Mediat 2017; 133: 20-8.
[http://dx.doi.org/10.1016/j.prostaglandins.2017.03.003] [PMID: 28347710]
[31]
Foudi N, Gomez I, Benyahia C, Longrois D, Norel X. Prostaglandin E2 receptor subtypes in human blood and vascular cells. Eur J Pharmacol 2012; 695(1-3): 1-6.
[http://dx.doi.org/10.1016/j.ejphar.2012.08.009] [PMID: 22964467]
[32]
Yuhki K, Kojima F, Kashiwagi H, et al. Roles of prostanoids in the pathogenesis of cardiovascular diseases: Novel insights from knockout mouse studies. Pharmacol Ther 2011; 129(2): 195-205.
[http://dx.doi.org/10.1016/j.pharmthera.2010.09.004] [PMID: 20920529]
[33]
Rocca B, Loeb AL, Strauss JF III, et al. Directed vascular expression of the thromboxane A2 receptor results in intrauterine growth retardation. Nat Med 2000; 6(2): 219-21.
[http://dx.doi.org/10.1038/72334] [PMID: 10655114]
[34]
Bolla M, You D, Loufrani L, et al. Cyclooxygenase involvement in thromboxane-dependent contraction in rat mesenteric resistance arteries. Hypertension 2004; 43(6): 1264-9.
[http://dx.doi.org/10.1161/01.HYP.0000127438.39744.07] [PMID: 15096470]
[35]
Pfister SL, Nithipatikom K, Campbell WB. Role of superoxide and thromboxane receptors in acute angiotensin II-induced vasoconstriction of rabbit vessels. Am J Physiol Heart Circ Physiol 2011; 300(6): H2064-71.
[http://dx.doi.org/10.1152/ajpheart.01135.2010] [PMID: 21460202]
[36]
Kobayashi T, Tahara Y, Matsumoto M, et al. Roles of thromboxane A(2) and prostacyclin in the development of atherosclerosis in apoE-deficient mice. J Clin Invest 2004; 114(6): 784-94.
[http://dx.doi.org/10.1172/JCI200421446] [PMID: 15372102]
[37]
Morrow JD, Hill KE, Burk RF, Nammour TM, Badr KF, Roberts LJ II. A series of prostaglandin F2-like compounds are produced in vivo in humans by a non-cyclooxygenase, free radical-catalyzed mechanism. Proc Natl Acad Sci USA 1990; 87(23): 9383-7.
[http://dx.doi.org/10.1073/pnas.87.23.9383] [PMID: 2123555]
[38]
Davies SS, Roberts LJ II. F2-isoprostanes as an indicator and risk factor for coronary heart disease. Free Radic Biol Med 2011; 50(5): 559-66.
[http://dx.doi.org/10.1016/j.freeradbiomed.2010.11.023] [PMID: 21126576]
[39]
Zhang ZJ. Systematic review on the association between F2-isoprostanes and cardiovascular disease. Ann Clin Biochem 2013; 50(Pt 2): 108-14.
[http://dx.doi.org/10.1258/acb.2012.011263] [PMID: 23019600]
[40]
Audoly LP, Rocca B, Fabre JE, et al. Cardiovascular responses to the isoprostanes iPF(2alpha)-III and iPE(2)-III are mediated via the thromboxane A(2) receptor in vivo. Circulation 2000; 101(24): 2833-40.
[http://dx.doi.org/10.1161/01.CIR.101.24.2833] [PMID: 10859290]
[41]
Cracowski JL. The putative role of isoprostanes in human cardiovascular physiology and disease: following the fingerprints. Heart 2003; 89(8): 821-2.
[http://dx.doi.org/10.1136/heart.89.8.821] [PMID: 12860842]
[42]
Minuz P, Andrioli G, Degan M, et al. The F2-isoprostane 8-epiprostaglandin F2alpha increases platelet adhesion and reduces the antiadhesive and antiaggregatory effects of NO. Arterioscler Thromb Vasc Biol 1998; 18(8): 1248-56.
[http://dx.doi.org/10.1161/01.ATV.18.8.1248] [PMID: 9714131]
[43]
Narumiya S, Sugimoto Y, Ushikubi F. Prostanoid receptors: structures, properties, and functions. Physiol Rev 1999; 79(4): 1193-226.
[http://dx.doi.org/10.1152/physrev.1999.79.4.1193] [PMID: 10508233]
[44]
Davidge ST. Prostaglandin H synthase and vascular function. Circ Res 2001; 89(8): 650-60.
[http://dx.doi.org/10.1161/hh2001.098351] [PMID: 11597987]
[45]
Jakobsson PJ, Morgenstern R, Mancini J, Ford-Hutchinson A, Persson B. Membrane-associated proteins in eicosanoid and glutathione metabolism (MAPEG). A widespread protein superfamily. Am J Respir Crit Care Med 2000; 161(2 Pt 2): S20-4.
[http://dx.doi.org/10.1164/ajrccm.161.supplement_1.ltta-5] [PMID: 10673221]
[46]
Wang M, Ihida-Stansbury K, Kothapalli D, et al. Microsomal prostaglandin e2 synthase-1 modulates the response to vascular injury. Circulation 2011; 123(6): 631-9.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.110.973685] [PMID: 21282500]
[47]
Wang M, Zukas AM, Hui Y, Ricciotti E, Puré E, FitzGerald GA. Deletion of microsomal prostaglandin E synthase-1 augments prostacyclin and retards atherogenesis. Proc Natl Acad Sci USA 2006; 103(39): 14507-12.
[http://dx.doi.org/10.1073/pnas.0606586103] [PMID: 16973753]
[48]
Chen L, Yang G, Monslow J, et al. Myeloid cell microsomal prostaglandin E synthase-1 fosters atherogenesis in mice. Proc Natl Acad Sci USA 2014; 111(18): 6828-33.
[http://dx.doi.org/10.1073/pnas.1401797111] [PMID: 24753592]
[49]
Chen L, Yang G, Xu X, et al. Cell selective cardiovascular biology of microsomal prostaglandin E synthase-1. Circulation 2013; 127(2): 233-43.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.112.119479] [PMID: 23204105]
[50]
Tang SY, Monslow J, R Grant G, et al. Cardiovascular consequences of prostanoid I receptor deletion in microsomal prostaglandin E synthase-1-deficient hyperlipidemic mice. Circulation 2016; 134(4): 328-38.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.116.022308] [PMID: 27440004]
[51]
Stables MJ, Gilroy DW. Old and new generation lipid mediators in acute inflammation and resolution. Prog Lipid Res 2011; 50(1): 35-51.
[http://dx.doi.org/10.1016/j.plipres.2010.07.005] [PMID: 20655950]
[52]
Nasrallah R, Hassouneh R, Hébert RL. pge2, kidney disease, and cardiovascular risk: beyond hypertension and diabetes. J Am Soc Nephrol 2016; 27(3): 666-76.
[http://dx.doi.org/10.1681/ASN.2015050528] [PMID: 26319242]
[53]
Psarra A, Nikolaou A, Kokotou MG, Limnios D, Kokotos G. Microsomal prostaglandin E2 synthase-1 inhibitors: a patent review. Expert Opin Ther Pat 2017; 27(9): 1047-59.
[http://dx.doi.org/10.1080/13543776.2017.1344218] [PMID: 28627961]
[54]
Francis SH, Blount MA, Corbin JD. Mammalian cyclic nucleotide phosphodiesterases: molecular mechanisms and physiological functions. Physiol Rev 2011; 91(2): 651-90.
[http://dx.doi.org/10.1152/physrev.00030.2010] [PMID: 21527734]
[55]
Morgado M, Cairrão E, Santos-Silva AJ, Verde I. Cyclic nucleotide-dependent relaxation pathways in vascular smooth muscle. Cell Mol Life Sci 2012; 69(2): 247-66.
[http://dx.doi.org/10.1007/s00018-011-0815-2] [PMID: 21947498]
[56]
Bobin P, Belacel-Ouari M, Bedioune I, et al. Cyclic nucleotide phosphodiesterases in heart and vessels: A therapeutic perspective. Arch Cardiovasc Dis 2016; 109(6-7): 431-43.
[http://dx.doi.org/10.1016/j.acvd.2016.02.004] [PMID: 27184830]
[57]
Ec-europa-eu. Annex I. Pharmaceutical forms, strengths of the medicinal products, routes of administration and marketing authorisation holders in the member states 2013. Available from. https://ec.europa.eu/health/documents/
[58]
Spinthakis N, Farag M, Rocca B, Gorog DA. More, more, more: reducing thrombosis in acute coronary syndromes beyond dual antiplatelet therapy-current data and future directions. J Am Heart Assoc 2018; 7(3) e007754
[http://dx.doi.org/10.1161/JAHA.117.007754] [PMID: 29374045]
[59]
Knecht T, Story J, Liu J, Davis W, Borlongan CV, Dela Peña IC. Adjunctive therapy approaches for ischemic stroke: Innovations to expand time window of treatment. Int J Mol Sci 2017; 18(12) E2756
[http://dx.doi.org/10.3390/ijms18122756] [PMID: 29257093]
[60]
de Donato G, Setacci F, Mele M, Giannace G, Galzerano G, Setacci C. Restenosis after coronary and peripheral intervention: Efficacy and clinical impact of cilostazol. Ann Vasc Surg 2017; 41: 300-7.
[http://dx.doi.org/10.1016/j.avsg.2016.08.050] [PMID: 28242395]
[61]
Coughlin SR. Protease-activated receptors in hemostasis, thrombosis and vascular biology. J Thromb Haemost 2005; 3(8): 1800-14.
[http://dx.doi.org/10.1111/j.1538-7836.2005.01377.x] [PMID: 16102047]
[62]
Fender AC, Rauch BH, Geisler T, Schrör K. Protease-activated receptor PAR-4: An inducible switch between thrombosis and vascular inflammation? Thromb Haemost 2017; 117(11): 2013-25.
[http://dx.doi.org/10.1160/TH17-03-0219] [PMID: 29044290]
[63]
Schrör K, Bretschneider E, Fischer K, et al. Thrombin receptors in vascular smooth muscle cells - function and regulation by vasodilatory prostaglandins. Thromb Haemost 2010; 103(5): 884-90.
[http://dx.doi.org/10.1160/TH09-09-0627] [PMID: 20143010]
[64]
McLaughlin JN, Patterson MM, Malik AB. Protease-activated receptor-3 (PAR3) regulates PAR1 signaling by receptor dimerization. Proc Natl Acad Sci USA 2007; 104(13): 5662-7.
[http://dx.doi.org/10.1073/pnas.0700763104] [PMID: 17376866]
[65]
Adams MN, Ramachandran R, Yau MK, et al. Structure, function and pathophysiology of protease activated receptors. Pharmacol Ther 2011; 130(3): 248-82.
[http://dx.doi.org/10.1016/j.pharmthera.2011.01.003] [PMID: 21277892]
[66]
Nieman MT. Protease-activated receptors in hemostasis. Blood 2016; 128(2): 169-77.
[http://dx.doi.org/10.1182/blood-2015-11-636472] [PMID: 27127302]
[67]
Davì G, Patrono C. Platelet activation and atherothrombosis. N Engl J Med 2007; 357(24): 2482-94.
[http://dx.doi.org/10.1056/NEJMra071014] [PMID: 18077812]
[68]
De Carlo M, Angelillis M, Liga R. Antithrombotic therapy for peripheral revascularisation. Curr Vasc Pharmacol 2020; 18: 223-35.
[http://dx.doi.org/10.2174/1570161117666190206234606]
[69]
Vrsalovic M, Aboyans V. Antithrombotic therapy in lower extremity artery disease. Curr Vasc Pharmacol 2020; 18: 215-22.
[PMID: 30727898]
[70]
Patrono C, Morais J, Baigent C, et al. antiplatelet agents for the treatment and prevention of coronary atherothrombosis. J Am Coll Cardiol 2017; 70(14): 1760-76.
[http://dx.doi.org/10.1016/j.jacc.2017.08.037] [PMID: 28958334]
[71]
Rocca B, Secchiero P, Ciabattoni G, et al. Cyclooxygenase-2 expression is induced during human megakaryopoiesis and characterizes newly formed platelets. Proc Natl Acad Sci USA 2002; 99(11): 7634-9.
[http://dx.doi.org/10.1073/pnas.112202999] [PMID: 12032335]
[72]
Dragani A, Pascale S, Recchiuti A, et al. The contribution of cyclooxygenase-1 and -2 to persistent thromboxane biosynthesis in aspirin-treated essential thrombocythemia: implications for antiplatelet therapy. Blood 2010; 115(5): 1054-61.
[http://dx.doi.org/10.1182/blood-2009-08-236679] [PMID: 19887674]
[73]
Chen H. Role of thromboxane A2 signaling in endothelium-dependent contractions of arteries. Prostaglandins Lipid Mediat 2018; 134: 32-7.
[http://dx.doi.org/10.1016/j.prostaglandins.2017.11.004] [PMID: 29180071]
[74]
Habib A, FitzGerald GA, Maclouf J. Phosphorylation of the thromboxane receptor alpha, the predominant isoform expressed in human platelets. J Biol Chem 1999; 274(5): 2645-51.
[http://dx.doi.org/10.1074/jbc.274.5.2645] [PMID: 9915793]
[75]
Fiessinger JN, Bounameaux H, Cairols MA, et al. Thromboxane antagonism with terutroban in peripheral arterial disease: the TAIPAD study. J Thromb Haemost 2010; 8(11): 2369-76.
[http://dx.doi.org/10.1111/j.1538-7836.2010.04020.x] [PMID: 20723034]
[76]
Bousser MG, Amarenco P, Chamorro A, et al. Terutroban versus aspirin in patients with cerebral ischaemic events (PERFORM): a randomised, double-blind, parallel-group trial. Lancet 2011; 377(9782): 2013-22.
[http://dx.doi.org/10.1016/S0140-6736(11)60600-4] [PMID: 21616527]
[77]
Smyth EM. Thromboxane and the thromboxane receptor in cardiovascular disease. Clin Lipidol 2010; 5(2): 209-19.
[http://dx.doi.org/10.2217/clp.10.11] [PMID: 20543887]
[78]
Sugimoto Y, Narumiya S. Prostaglandin E receptors. J Biol Chem 2007; 282(16): 11613-7.
[http://dx.doi.org/10.1074/jbc.R600038200] [PMID: 17329241]
[79]
Petrucci G, De Cristofaro R, Rutella S, et al. Prostaglandin E2 differentially modulates human platelet function through the prostanoid EP2 and EP3 receptors. J Pharmacol Exp Ther 2011; 336(2): 391-402.
[http://dx.doi.org/10.1124/jpet.110.174821] [PMID: 21059804]
[80]
Gross S, Tilly P, Hentsch D, Vonesch JL, Fabre JE. Vascular wall-produced prostaglandin E2 exacerbates arterial thrombosis and atherothrombosis through platelet EP3 receptors. J Exp Med 2007; 204(2): 311-20.
[http://dx.doi.org/10.1084/jem.20061617] [PMID: 17242161]
[81]
Tilly P, Charles AL, Ludwig S, et al. Blocking the EP3 receptor for PGE2 with DG-041 decreases thrombosis without impairing haemostatic competence. Cardiovasc Res 2014; 101(3): 482-91.
[http://dx.doi.org/10.1093/cvr/cvt276] [PMID: 24323317]
[82]
Burnstock G, Ralevic V. Purinergic signaling and blood vessels in health and disease. Pharmacol Rev 2013; 66(1): 102-92.
[http://dx.doi.org/10.1124/pr.113.008029] [PMID: 24335194]
[83]
Burnstock G. Purinergic signalling: from discovery to current developments. Exp Physiol 2014; 99(1): 16-34.
[http://dx.doi.org/10.1113/expphysiol.2013.071951] [PMID: 24078669]
[84]
Jagroop IA, Burnstock G, Mikhailidis DP. Both the ADP receptors P2Y1 and P2Y12, play a role in controlling shape change in human platelets. Platelets 2003; 14(1): 15-20.
[http://dx.doi.org/10.1080/0953710021000062914] [PMID: 12623443]
[85]
Burnstock G. Purinergic signaling in the cardiovascular system. Circ Res 2017; 120(1): 207-28.
[http://dx.doi.org/10.1161/CIRCRESAHA.116.309726] [PMID: 28057794]
[86]
Gurbel PA, Kuliopulos A, Tantry US. G-protein-coupled receptors signaling pathways in new antiplatelet drug development. Arterioscler Thromb Vasc Biol 2015; 35(3): 500-12.
[http://dx.doi.org/10.1161/ATVBAHA.114.303412] [PMID: 25633316]
[87]
Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007; 357(20): 2001-15.
[http://dx.doi.org/10.1056/NEJMoa0706482] [PMID: 17982182]
[88]
Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361(11): 1045-57.
[http://dx.doi.org/10.1056/NEJMoa0904327] [PMID: 19717846]
[89]
Vranckx P, Valgimigli M, Jüni P, et al. Ticagrelor plus aspirin for 1 month, followed by ticagrelor monotherapy for 23 months vs aspirin plus clopidogrel or ticagrelor for 12 months, followed by aspirin monotherapy for 12 months after implantation of a drug-eluting stent: a multicentre, open-label, randomised superiority trial. Lancet 2018; 392(10151): 940-9.
[http://dx.doi.org/10.1016/S0140-6736(18)31858-0] [PMID: 30166073]
[90]
Dunne H, Cowman J, Kenny D. MRS2179: a novel inhibitor of platelet function. BMC Proc 2015; 9(Suppl. 1): A2.
[http://dx.doi.org/10.1186/1753-6561-9-S1-A2]
[91]
Yanachkov IB, Chang H, Yanachkova MI, et al. New highly active antiplatelet agents with dual specificity for platelet P2Y1 and P2Y12 adenosine diphosphate receptors. Eur J Med Chem 2016; 107: 204-18.
[http://dx.doi.org/10.1016/j.ejmech.2015.10.055] [PMID: 26588064]
[92]
Tricoci P, Huang Z, Held C, et al. Thrombin-receptor antagonist vorapaxar in acute coronary syndromes. N Engl J Med 2012; 366(1): 20-33.
[http://dx.doi.org/10.1056/NEJMoa1109719] [PMID: 22077816]
[93]
Judge HM, Jennings LK, Moliterno DJ, et al. PAR1 antagonists inhibit thrombin-induced platelet activation whilst leaving the PAR4-mediated response intact. Platelets 2015; 26(3): 236-42.
[http://dx.doi.org/10.3109/09537104.2014.902924] [PMID: 24750101]
[94]
ClinicalTrials.gov. Safety and efficacy study of a protease activated receptor-4 antagonist being tested to reduce the chances of having additional strokes or "mini strokes" 2016. Available from:. https://clinicaltrials.gov/ct2/show/NCT02671461
[95]
Agbani EO, Poole AW. Procoagulant platelets: generation, function, and therapeutic targeting in thrombosis. Blood 2017; 130(20): 2171-9.
[http://dx.doi.org/10.1182/blood-2017-05-787259] [PMID: 28972013]
[96]
Eikelboom JW, Connolly SJ, Bosch J, et al. Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease. N Engl J Med 2017; 377(14): 1319-30.
[http://dx.doi.org/10.1056/NEJMoa1709118] [PMID: 28844192]
[97]
Esmon CT. Targeting factor Xa and thrombin: impact on coagulation and beyond. Thromb Haemost 2014; 111(4): 625-33.
[http://dx.doi.org/10.1160/TH13-09-0730] [PMID: 24336942]
[98]
Cleator JH, Zhu WQ, Vaughan DE, Hamm HE. Differential regulation of endothelial exocytosis of P-selectin and von Willebrand factor by protease-activated receptors and cAMP. Blood 2006; 107(7): 2736-44.
[http://dx.doi.org/10.1182/blood-2004-07-2698] [PMID: 16332977]
[99]
Laurent M, Joimel U, Varin R, et al. Comparative study of the effect of rivaroxaban and fondaparinux on monocyte’s coagulant activity and cytokine release. Exp Hematol Oncol 2014; 3(1): 30.
[http://dx.doi.org/10.1186/2162-3619-3-30] [PMID: 25601900]
[100]
Rosenkranz AC, Schrör K, Rauch BH. Direct inhibitors of thrombin and factor Xa attenuate clot-induced mitogenesis and inflammatory gene expression in human vascular smooth muscle cells. Thromb Haemost 2011; 106(3): 561-2.
[http://dx.doi.org/10.1160/TH11-04-0275] [PMID: 21800011]
[101]
Wong PC, Jiang X. Apixaban, a direct factor Xa inhibitor, inhibits tissue-factor induced human platelet aggregation in vitro: comparison with direct inhibitors of factor VIIa, XIa and thrombin. Thromb Haemost 2010; 104(2): 302-10.
[PMID: 20589316]
[102]
Hosokawa K, Ohnishi T, Sameshima H, et al. Comparative evaluation of direct thrombin and factor Xa inhibitors with antiplatelet agents under flow and static conditions: an in vitro flow chamber model. PLoS One 2014; 9(1) e86491
[http://dx.doi.org/10.1371/journal.pone.0086491] [PMID: 24497951]
[103]
Graff J, von Hentig N, Misselwitz F, et al. Effects of the oral, direct factor xa inhibitor rivaroxaban on platelet-induced thrombin generation and prothrombinase activity. J Clin Pharmacol 2007; 47(11): 1398-407.
[http://dx.doi.org/10.1177/0091270007302952] [PMID: 17873238]
[104]
Posma JJ, Posthuma JJ, Spronk HM. Coagulation and non-coagulation effects of thrombin. J Thromb Haemost 2016; 14(10): 1908-16.
[http://dx.doi.org/10.1111/jth.13441] [PMID: 27513692]
[105]
Zhou Q, Bea F, Preusch M, et al. Evaluation of plaque stability of advanced atherosclerotic lesions in apo E-deficient mice after treatment with the oral factor Xa inhibitor rivaroxaban. Mediators Inflamm 2011; 2011 432080
[http://dx.doi.org/10.1155/2011/432080] [PMID: 21772662]
[106]
Sparkenbaugh EM, Chantrathammachart P, Mickelson J, et al. Differential contribution of FXa and thrombin to vascular inflammation in a mouse model of sickle cell disease. Blood 2014; 123(11): 1747-56.
[http://dx.doi.org/10.1182/blood-2013-08-523936] [PMID: 24449213]
[107]
Patrono C, Rocca B. The future of antiplatelet therapy in cardiovascular disease. Annu Rev Med 2010; 61: 49-61.
[http://dx.doi.org/10.1146/annurev-med-020209-171035] [PMID: 20059331]
[108]
Patrono C, Rocca B, De Stefano V. Platelet activation and inhibition in polycythemia vera and essential thrombocythemia. Blood 2013; 121(10): 1701-11.
[http://dx.doi.org/10.1182/blood-2012-10-429134] [PMID: 23335367]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 18
ISSUE: 3
Year: 2020
Published on: 06 February, 2019
Page: [204 - 214]
Pages: 11
DOI: 10.2174/1570161117666190206234046
Price: $65

Article Metrics

PDF: 32
HTML: 8
EPUB: 2
PRC: 1