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Enhanced P-selectin expression on platelet-a marker of platelet activation, in young patients with angiographically proven coronary artery disease

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Abstract

P-selectin (CD62p) exposure is an established marker for platelet activation. P-selectin exposure can trigger variety of thrombotic and inflammatory reactions. In patients with coronary artery disease (CAD), platelets are activated, and hence, there is increased P-selectin exposure. The role of P-selectin exposure in patients on treatment with statins and anti-platelets is conflicting. A case–control study was performed to determine P-selectin exposure in consecutively recruited 142 patients (age ≤ 55 years) with angiographically proven CAD on treatment and 92 asymptomatic controls. P-selectin exposure was determined by flow cytometry. Data on conventional risk factors were obtained along with estimation of levels of thrombotic [fibrinogen, lipoprotein (a), tissue plasminogen activator, plasminogen activator inhibitor-1, homocysteine and von Willebrand factor] and anti-thrombotic factors (antithrombin III). The P-selectin exposure was compared among patient groups who had different modes of presentation of CAD and categories of CAD disease severity. The patients were followed up for a period of 26 months. The results indicate that P-selectin exposure was significantly elevated in patients (mean ± SD 9.24 ± 11.81) compared to controls (mean ± SD 1.48 ± 2.85) with p < 0.0001. Similarly, conventional risk factors were significantly elevated in patients. P-selectin exposure showed significant negative correlation with antithrombin III levels. P-selectin exposure was higher in patients who presented with acute coronary syndromes than those who presented with effort angina. Cardiovascular event rate was 6 % on follow-up. The study establishes that thrombotic–inflammatory pathways enhancing P-selectin exposure unrelated to treatment might be activated in patients, while the event rate remained lowered, and hence, treatment strategies should be inclusive to control these factors.

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References

  1. Davì G, Patrono C (2007) Platelet activation and atherothrombosis. N Engl J Med 357:2482–2494. doi:10.1056/NEJMra071014

    Article  PubMed  Google Scholar 

  2. Passacquale G, Vamadevan P, Pereira L, Hamid C, Corrigall V, Ferro A (2011) Monocyte-platelet interaction induces a pro-inflammatory phenotype in circulating monocytes. PLoS One 6:e25595. doi:10.1371/journal.pone.0025595

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Ludwig RJ, Schön MP, Boehncke W-H (2007) P-selectin: a common therapeutic target for cardiovascular disorders, inflammation and tumour metastasis. Expert Opin Ther Targets 11:1103–1117. doi:10.1517/14728222.11.8.1103

    Article  CAS  PubMed  Google Scholar 

  4. Ramachandran J, Rubenstein D, Bluestein D, Jesty J (2004) Activation of platelets exposed to shear stress in the presence of smoke extracts of low-nicotine and zero-nicotine cigarettes: the protective effect of nicotine. Nicotine Tob Res Off J Soc Res Nicotine Tob 6:835–841

    Article  CAS  Google Scholar 

  5. Deepa R, Mohan V, Premanand C, Rajan VS, Karkuzhali K, Velmurugan K, Agarwal S, Gross MD, Markovitz J (2006) Accelerated platelet activation in Asian Indians with diabetes and coronary artery disease—The Chennai Urban Population Study (CUPS-13). J Assoc Physicians India 54:704–708

    CAS  PubMed  Google Scholar 

  6. Ridker PM, Buring JE, Rifai N (2001) Soluble P-selectin and the risk of future cardiovascular events. Circulation 103:491–495. doi:10.1161/01.CIR.103.4.491

    Article  CAS  PubMed  Google Scholar 

  7. Vazzana N, Ganci A, Cefalu AB, Lattanzio S, Noto D, Santoro N, Saggini R, Puccetti L, Averna M, Davi G (2013) Enhanced lipid peroxidation and platelet activation as potential contributors to increased cardiovascular risk in the low-HDL phenotype. J Am Heart Assoc 2:e000063–e000063. doi:10.1161/JAHA.113.000063

    Article  PubMed  PubMed Central  Google Scholar 

  8. Lip GYH (2003) Hypertension, platelets, and the endothelium: the “thrombotic paradox” of hypertension (or “birmingham paradox”) revisited. Hypertension 41:199–200. doi:10.1161/01.HYP.0000049761.98155.7B

    Article  CAS  PubMed  Google Scholar 

  9. Sekhri T, Kanwar RS, Wilfred R, Chugh P, Chhillar M, Aggarwal R, Sharma YK, Sethi J, Sundriyal J, Bhadra K, Singh S, Rautela N, Chand T, Singh M, Singh SK (2014) Prevalence of risk factors for coronary artery disease in an urban Indian population. BMJ Open 4:e005346–e005346. doi:10.1136/bmjopen-2014-005346

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. George R, Sivadasanpillai H, Jayakumari N, Bhatt A, Thulaseedharan JV, Tharakan JA (2015) Circulating thrombotic risk factors in young patients with coronary artery disease who are on statins and anti-platelet drugs. Indian J Clin Biochem. doi:10.1007/s12291-015-0540-y

    PubMed  Google Scholar 

  11. Banerjee M, Siddique S, Mukherjee S, Roychoudhury S, Das P, Ray MR, Lahiri T (2012) Hematological, immunological, and cardiovascular changes in individuals residing in a polluted city of India: a study in Delhi. Int J Hyg Environ Health 215:306–311. doi:10.1016/j.ijheh.2011.08.003

    Article  CAS  PubMed  Google Scholar 

  12. Capodanno D, Angiolillo DJ (2013) Management of antiplatelet therapy in patients with coronary artery disease requiring cardiac and noncardiac surgery. Circulation 128:2785–2798. doi:10.1161/CIRCULATIONAHA.113.003675

    Article  PubMed  Google Scholar 

  13. Members Writing Committee, Jneid H, Anderson JL, Wright RS, Adams CD, Bridges CR, Casey DE et al (2012) 2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non-ST-elevation myocardial infarction (updating the 2007 guideline and replacing the 2011 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 126:875–910. doi:10.1161/CIR.0b013e318256f1e0

    Article  Google Scholar 

  14. American Diabetes Association (2014) Diagnosis and classification of diabetes mellitus. Diabetes Care 37:S81–S90. doi:10.2337/dc14-S081

    Article  Google Scholar 

  15. Stone NJ, Robinson J, Lichtenstein AH, Merz CNB, Blum CB, Eckel RH et al (2013) 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. doi:10.1161/01.cir.0000437738.63853.7a

    Google Scholar 

  16. Members Writing Committee, Drozda J, Messer JV, Spertus J, Abramowitz B, Alexander K et al (2011) ACCF/AHA/AMA-PCPI 2011 performance measures for adults with coronary artery disease and hypertension: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Performance Measures and the American Medical Association–Physician Consortium for Performance Improvement. Circulation 124:248–270. doi:10.1161/CIR.0b013e31821d9ef2

    Article  Google Scholar 

  17. Scheuner MT, Whitworth WC, McGruder H, Yoon PW, Khoury MJ (2006) Expanding the definition of a positive family history for early-onset coronary heart disease. Genet Med 8:491–501. doi:10.1097/01.gim.0000232582.91028.03

    Article  PubMed  Google Scholar 

  18. Michelson AD (1996) Flow cytometry: a clinical test of platelet function. Blood 87:4925–4936

    CAS  PubMed  Google Scholar 

  19. Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18:499–502

    CAS  PubMed  Google Scholar 

  20. Ferroni P, Riondino S, Vazzana N, Santoro N, Guadagni F, Davì G (2012) Biomarkers of platelet activation in acute coronary syndromes. Thromb Haemost 108:1109–1123. doi:10.1160/TH12-08-0550

    Article  PubMed  Google Scholar 

  21. Badimon L, Padro T, Vilahur G (2012) Atherosclerosis, platelets and thrombosis in acute ischaemic heart disease. Eur Heart J Acute Cardiovasc Care 1:60–74. doi:10.117/2048872612441582

    PubMed  PubMed Central  Google Scholar 

  22. Gokulakrishnan K, Deepa R, Mohan V, Gross MD (2006) Soluble P-selectin and CD40L levels in subjects with prediabetes, diabetes mellitus, and metabolic syndrome—the Chennai Urban Rural Epidemiology Study. Metabolism 55:237–242. doi:10.1016/j.metabol.2005.08.019

    Article  CAS  PubMed  Google Scholar 

  23. Patel RT, Lev EI, Vaduganathan M, Guthikonda S, Bergeron A, Maresh K, Dong J-F, Kleiman NS (2007) Platelet reactivity among Asian Indians and Caucasians. Platelets 18:261–265. doi:10.1080/09537100701235716

    Article  CAS  PubMed  Google Scholar 

  24. Linden MD, Furman MI, Frelinger AL 3rd, Fox ML, Barnard MR, Li Y, Przyklenk K, Michelson AD (2007) Indices of platelet activation and the stability of coronary artery disease. J Thromb Haemost 5:761–765. doi:10.1111/j.1538-7836.2007.02462.x

    Article  CAS  PubMed  Google Scholar 

  25. Kontush A (2014) HDL-mediated mechanisms of protection in cardiovascular disease. Cardiovasc Res 103:341–349. doi:10.1093/cvr/cvu147

    Article  CAS  PubMed  Google Scholar 

  26. Pernerstorfer T, Stohlawetz P, Stummvoll G, Kapiotis G, Szekeres T, Eichler HG, Jilma B (1998) Low-dose aspirin does not lower in vivo platelet activation in healthy smokers. Br J Haematol 102:1229–1231

    Article  CAS  PubMed  Google Scholar 

  27. Levi M (2004) Bidirectional relation between inflammation and coagulation. Circulation 109:2698–2704. doi:10.1161/01.CIR.0000131660.51520.9A

    Article  PubMed  Google Scholar 

  28. Oelschläger C, Römisch J, Staubitz A, Stauss H, Leithäuser B, Tillmanns H, Hölschermann H (2002) Antithrombin III inhibits nuclear factor κB activation in human monocytes and vascular endothelial cells. Blood 99:4015–4020. doi:10.1182/blood.V99.11.4015

    Article  PubMed  Google Scholar 

  29. Tan KT, Tayebjee MH, MacFadyen RJ, Lip GYH (2005) Relation of platelet activation to coronary angiographic severity and collateralization. Am J Cardiol 96:208–210. doi:10.1016/j.amjcard.2005.03.045

    Article  CAS  PubMed  Google Scholar 

  30. Stellos K, Bigalke B, Stakos D, Henkelmann N, Gawaz M (2010) Platelet-bound P-selectin expression in patients with coronary artery disease: impact on clinical presentation and myocardial necrosis, and effect of diabetes mellitus and anti-platelet medication. J Thromb Haemost 8:205–207. doi:10.1111/j.1538-7836.2009.03659.x

    Article  CAS  PubMed  Google Scholar 

  31. Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, Ramírez C, Sabaté M, Jimenez-Quevedo P et al (2005) Platelet function profiles in patients with type 2 diabetes and coronary artery disease on combined aspirin and clopidogrel treatment. Diabetes 54:2430–2435

    Article  CAS  PubMed  Google Scholar 

  32. Zaleski A, Capizzi J, Ballard KD, Troyanos C, Baggish A, D’Hemecourt P, Thompson PD, Parker B (2013) Statins attenuate the increase in P-selectin produced by prolonged exercise. J Sports Med 2013:1–5. doi:10.1155/2013/487567

    Article  Google Scholar 

  33. Popović M, Smiljanić K, Dobutović B, Syrovets T, Simmet T, Isenović ER (2012) Thrombin and vascular inflammation. Mol Cell Biochem 359:301–313. doi:10.1007/s11010-011-1024-x

    Article  PubMed  Google Scholar 

  34. Aukrust P, Halvorsen B, Ueland T, Michelsen AE, Skjelland M, Gullestad L, Yndestad A, Otterdal K (2010) Activated platelets and atherosclerosis. Expert Rev Cardiovasc Ther 8:1297–1307. doi:10.1586/erc.10.92

    Article  PubMed  Google Scholar 

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Acknowledgments

Authors wish to thank Dr. Lissy K. Krishnan and all staff of Thrombosis Research Unit (SCTIMST) for providing facilities to conduct experiments related to thrombotic risk factors and flow cytometry for P-selectin analysis. Help rendered by all staff of Central Clinical Lab—Department of Biochemistry and Department of Cardiology (SCTIMST)—is also acknowledged. The grant provided by Kerala State Council for Science, Technology and Environment, Pattom P.O. Thiruvananthapuram, Kerala, India (File No.: 041/SRSLS/07/CSTE), for the work is greatly acknowledged. Ms. Reema George received the Junior Research Fellowship and now receiving Senior Research Fellowship from Council of Scientific and Industrial Research (CSIR), Pusa, New Delhi, India, Pin: 110001 (File No.: 09/523(0075)/2011-EMR-I).

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Correspondence to Harikrishnan Sivadasanpillai.

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George, R., Bhatt, A., Narayani, J. et al. Enhanced P-selectin expression on platelet-a marker of platelet activation, in young patients with angiographically proven coronary artery disease. Mol Cell Biochem 419, 125–133 (2016). https://doi.org/10.1007/s11010-016-2756-4

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