Thrombopoietin Contributes to Enhanced Platelet Activation in Patients With Unstable Angina

• Published in: Journal of the American College of Cardiology Vol. 48; no. 11; pp. 2195 - 2203
• Main Authors: Lupia, Enrico, Bosco, Ornella, Bergerone, Serena, Dondi, Anna Erna, Goffi, Alberto, Oliaro, Elena, Cordero, Marco, Del Sorbo, Lorenzo, Trevi, Giampaolo, Montrucchio, Giuseppe
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 05-12-2006; Elsevier Science; Elsevier Limited
• Subjects: Acute coronary syndromes; Aged; Angina, Unstable - blood; Biological and medical sciences; Blood diseases; Blood platelets; Blood Platelets - drug effects; Blood Platelets - metabolism; Cardiology; Cardiology. Vascular system; Cardiovascular disease; Coronary heart disease; Coronary vessels; Diabetes; Drug therapy; Enzymes; Female; Heart; Heart attacks; Humans; In Vitro Techniques; Male; Medical sciences; Middle Aged; Monocytes; Platelet Activation; Receptors, Thrombopoietin - blood; Recombinant Proteins - pharmacology; Thrombopoietin - blood; Thrombopoietin - pharmacology; CRP; TPO; TPOR; PI; rhTPO; UA; ADP; SA; EPI; PRP; Human; Platelet; Cardiovascular disease; Patient; Activation; Circulatory system; Cardiology; Coronary heart disease; Variant angina; Phlebology; Thrombopoietin
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2006.04.106

Thrombopoietin Contributes to Enhanced Platelet Activation in Patients With Unstable Angina
Enrico Lupia, Ornella Bosco, Serena Bergerone, Anna Erna Dondi, Alberto Goffi, Elena Oliaro, Marco Cordero, Lorenzo Del Sorbo, Giampaolo Trevi, Giuseppe Montrucchio
We investigated the potential role of circulating thrombopoietin (TPO) in platelet activation during unstable angina (UA). We found that patients with UA showed elevated circulating TPO levels, as well as increased monocyte-platelet binding, platelet P-selectin expression, and C-reactive protein levels. The UA patients also showed reduced platelet expression of the TPO receptor, c-Mpl. In vitro, plasma from UA patients, but not from stable angina patients or healthy control subjects, primed platelet aggregation and monocyte-platelet binding, which were both reduced when an inhibitor of TPO was used. Thrombopoietin may therefore enhance platelet activation during UA, potentially participating in the pathogenesis of acute coronary syndromes.
We sought to investigate the potential role of elevated levels of thrombopoietin (TPO) in platelet activation during unstable angina (UA).
Thrombopoietin is a humoral growth factor that does not induce platelet aggregation per se, but primes platelet activation in response to several agonists. No data concerning its contribution to platelet function abnormalities described in patients with UA are available.
We studied 15 patients with UA and, as controls, 15 patients with stable angina (SA) and 15 healthy subjects. We measured TPO and C-reactive protein (CRP), as well as monocyte-platelet binding and the platelet expression of P-selectin and of the TPO receptor, c-Mpl. The priming activity of patient or control plasma on platelet aggregation and monocyte-platelet binding and the role of TPO in this effect also were studied.
Patients with UA showed higher circulating TPO levels, as well as increased monocyte-platelet binding, platelet P-selectin expression, and CRP levels, than those with SA and healthy control subjects. The UA patients also showed reduced platelet expression of the TPO receptor, c-Mpl. In vitro, the plasma from UA patients, but not from SA patients or healthy controls, primed platelet aggregation and monocyte-platelet binding, which were both reduced when an inhibitor of TPO was used.
Thrombopoietin may enhance platelet activation in the early phases of UA, potentially participating in the pathogenesis of acute coronary syndromes.