Advances in Clinical and Experimental Medicine
2014, vol. 23, nr 2, March-April, p. 159–167
Publication type: original article
Expression of the PAR-1 Protein on the Surface of Platelets in Patients with Chronic Peripheral Arterial Insufficiency – Preliminary Report
1 Department and Clinic of angiology, Hypertension and diabetology, Wroclaw Medical University, Poland
2 Molecular Techniques Unit, Wroclaw Medical University, Poland
3 Department and Clinic of Ophthalmology, Wroclaw Medical University, Poland
Background. The activation of pro-coagulation mechanisms associated with the vascular wall’s immune and inflammatory responses wall to injury plays a crucial role in the mechanisms of the induction and progression of atherosclerosis.
Objectives. The aim of this study was to determine the role of protease activated receptors (PaR-1) expressed on the surface of blood platelets in the pathogenesis of chronic peripheral arterial obliterative disease (PaOd) in patients with obliterative atherosclerosis (n = 24) and diabetic macroangiopathy (n = 16), as well as in the controls (n = 12).
Material and Methods. In addition to the expression of PaR-1, serum/plasma concentrations of thrombin-antithrombin complex (TaT), the von Willebrand factor (vWf), the platelet-derived growth factor, monocyte chemotactic protein, the soluble form of the platelet endothelial cell adhesion molecule, thrombin activatable fibrinolysis inhibitor and interleukin 6 (IL-6) were determined.
Results. Compared to the controls, PaOd patients were characterized by significantly higher levels of PaR-1 expression, vWf, TaT and IL-6. Individuals with diabetic macroangiopathy did not differ significantly from individuals with obliterative atherosclerosis in terms of PaR-1 expression. Upon activation with thrombin receptor antagonist peptide (TRaP), the levels of PaR-1 were comparable in all analyzed groups. In patients with diabetic macroangiopathy, a significant association was observed between the expression of PaR-1 on the surface of the platelet and the serum TaT concentration, as well as between TaT and serum IL-6 concentration.
Conclusion. enhanced expression of PaR-1 on the thrombocyte surface in chronic PaOd patients occurs equally in cases of diabetic macroangiopathy and in individuals free from this endocrine pathology.
adhesion molecules, diabetic macroangiopathy, obliterative atherosclerosis, PaR-1.
- Jennings LK: Role of platelets in atherothrombosis. am J Cardiol 2009, 103, 4–10.
- Bombeli T, Schwartz BR, Harlan JM: adhesion of activated platelets to endothelial cells: evidence for a GPIIbIIIa-dependent bridging mechanism and novel roles for endothelial intercellular adhesion molecule 1 (ICaM-1), alphavbeta3 integrin, and GPIbalpha. J exp Med 1998, 187, 329–339.
- Boulbou MS, Koukoulis GN, Vasiou KG, Petinaki EA, Gourgoulianis KI, Fezoulidis IB: Increased soluble e-selectin levels in type 2 diabetic patients with peripheral arterial disease. Int angiol 2004, 23, 18–24.
- Ross R: atherosclerosis-an inflammatory disease. N engl J Med 1999, 340, 115–126.
- Vergnolle N, Wallace JL, Bunnett NW, Hollenberg MD: Protease-activated receptors in inflammation, neuronal signaling and pain. Trends Pharmacol Sci 2001, 22, 146–152.
- Dembinska-Kiec A, Naskalski JW: diagnostyka laboratoryjna z elementami biochemii klinicznej. elsevier Urban & Partner, Wrocław 2009.
- Traynelis SF, Trejo J: Protease-activated receptor signaling: new roles and regulatory mechanisms. Curr Opin Hematol 2007, 14, 230–235.
- Hron G, Kollars M, Weber H, Sagaster V, Quehenberger P, Eichinger S, Kyrle PA, Weltermann A: Tissue factor-positive microparticles: cellular origin and association with coagulation activation in patients with colorectal cancer. Thromb Haemost 2007, 97, 119–123.
- Coughlin SR: Thrombin signalling and protease-activated receptors. Nature 2000, 407, 258–264.
- Martorell L, Martinez-Gonzalez J, Rodriguez C, Gentile M, Calvayrac O, Badimon L: Thrombin and proteaseactivated receptors (PaRs) in atherothrombosis. Thromb Haemost 2008, 99, 305–315.
- Chieng-Yane P, Bocquet A, Letienne R, Bourbon T, Sablayrolles S, Perez M, Hatem SN, Lompre AM, Le Grand B, David-Dufilho M: Protease-activated receptor-1 antagonist f 16618 reduces arterial restenosis by down-regulation of tumor necrosis factor alpha and matrix metalloproteinase 7 expression, migration, and proliferation of vascular smooth muscle cells. J Pharmacol exp Ther 2011, 336, 643–651.
- Nadal-Wollbold F, Bocquet A, Bourbon T, Letienne R, Le Grand B: Protease-activated receptor 1 antagonists prevent platelet aggregation and adhesion without affecting thrombin time. eur J Pharmacol 2010, 644, 188–194.
- O’Donoghue ML, Bhatt DL, Wiviott SD, Goodman SG, Fitzgerald DJ, Angiolillo DJ, Goto S, Montalescot G, Zeymer U, Aylward PE, Guetta V, Dudek D, Ziecina R, Contant CF, Flather MD, Investigators L-A: Safety and tolerability of atopaxar in the treatment of patients with acute coronary syndromes: the lessons from antagonizing the cellular effects of Thrombin-acute Coronary Syndromes Trial. Circulation 2011, 123, 1843–1853.
- Vane JR, Botting RM: The mechanism of action of aspirin. Thromb Res 2003, 110, 255–258.
- Undas A, Stepien E, Branicka A, Wolkow P, Zmudka K, Tracz W: Thrombin formation and platelet activation at the site of vascular injury in patients with coronary artery disease treated with clopidogrel combined with aspirin. Kardiol Pol 2009, 67, 591–598.
- Wallinder J, Bergqvist D, Henriksson AE: Haemostatic markers in patients with abdominal aortic aneurysm and the impact of aneurysm size. Thromb Res 2009, 124, 423–426.
- Gosk-Bierska I, Adamiec R, Alexewicz P, Wysokinski WE: Coagulation in diabetic and non-diabetic claudicants. Int angiol 2002, 21, 128–133.
- Leger AJ, Covic L, Kuliopulos A: Protease-activated receptors in cardiovascular diseases. Circulation 2006, 114, 1070–1077.
- Hamilton JR: Protease-activated receptors as targets for antiplatelet therapy. Blood Rev 2009, 23, 61–65.
- Gosk-Bierska I, Adamiec R, Szuba A: Platelets’ glycoproteins and their ligands in patients with intermittent claudication. Int angiol 2003, 22, 164–171.
- Gosk-Bierska I, Adamiec R: The role of platelet glycoprotein receptors and their ligands: fibrinogen and von Willebrand factor in arterial thrombosis. Przegl Lek 2003, 60, 485–488.
- Ott I, Neumann FJ, Gawaz M, Schmitt M, Schömig A: Increased neutrophil-platelet adhesion in patients with unstable angina. Circulation 1996, 94, 1239–1246.
- Yakushkin VV, Zyuryaev IT, Khaspekova SG, Sirotkina OV, Ruda MY, Mazurov AV: Glycoprotein IIb–IIIa content and platelet aggregation in healthy volunteers and patients with acute coronary syndrome. Platelets 2011, 22, 243–251.
- Sutkowska E, Wozniewski M, Gamian A, Gosk-Bierska I, Alexewicz P, Sutkowski K, Wysokinski WE: Intermittent pneumatic compression in stable claudicants: effect on hemostasis and endothelial function. Int angiol 2009, 28, 373–379.