Thrombopoietin contributes to enhanced platelet activation in cigarette smokers

• Published in: Atherosclerosis Vol. 210; no. 1; pp. 314 - 319
• Main Authors: Lupia, Enrico, Bosco, Ornella, Goffi, Alberto, Poletto, Cesare, Locatelli, Stefania, Spatola, Tiziana, Cuccurullo, Alessandra, Montrucchio, Giuseppe
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ireland Ltd 01-05-2010; Elsevier
• Subjects: Adult; Angina; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Blood coagulation. Blood cells; C-Reactive Protein - analysis; Cardiology. Vascular system; Cardiovascular; Case-Control Studies; Cell Aggregation - physiology; Cotinine - blood; Female; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Humans; Leukocyte–platelet adhesion; Male; Medical sciences; Molecular and cellular biology; P-Selectin - blood; Platelet; Platelet Activation - physiology; Platelet activation markers; Platelet aggregation; Smoking; Smoking - physiopathology; Smoking Cessation; Thrombopoietin; Thrombopoietin - blood; Thrombopoietin - physiology; Platelet activation markers; Platelet aggregation; Leukocyte–platelet adhesion; Thrombopoietin; Smoking; Leukocyte-platelet adhesion; Leukocyte; Tobacco smoking; Cardiovascular disease; Vascular disease; Aggregation; Cigarette; Platelet; Smoker; Atherosclerosis
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2009.11.019

Abstract Objectives : Thrombopoietin (TPO) is a humoral growth factor that primes platelet activation in response to several agonists. We recently showed that TPO enhances platelet activation in unstable angina and sepsis. Aim of this study was to investigate the role of TPO in platelet function abnormalities described in cigarette smokers. Methods : In a case–control study we enrolled 20 healthy cigarette smokers and 20 nonsmokers, and measured TPO and C-reactive protein (CRP), as well as platelet–leukocyte binding and P-selectin expression. In vitro we evaluated the priming activity of smoker or control plasma on platelet activation, and the role of TPO in this effect. We then studied the effects of acute smoking and smoking cessation on TPO levels and platelet activation indices. Results : Chronic cigarette smokers had higher circulating TPO levels than nonsmoking controls, as well as increased platelet–leukocyte binding, P-selectin expression, and CRP levels. Serum cotinine concentrations correlated with TPO concentrations, platelet–monocyte aggregates and P-selectin expression. In addition, TPO levels significantly correlated with ex vivo platelet–monocyte aggregation and P-selectin expression. In vitro , the plasma from cigarette smokers, but not from nonsmoking controls, primed platelet–monocyte binding, which was reduced when an inhibitor of TPO was used. We also found that acute smoking slightly increased TPO levels, but did not affect platelet–leukocyte binding, whereas smoking cessation induced a significant decrease in both circulating TPO and platelet–leukocyte aggregation. Conclusion : Elevated TPO contributes to enhance platelet activation and platelet–monocyte cross-talk in cigarette smokers.