Thrombopoietin contributes to enhanced platelet activation in patients with unstable angina.
OBJECTIVE
We sought to investigate the potential role of elevated levels of thrombopoietin (TPO) in platelet activation during unstable angina (UA).


BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Thrombopoietin may enhance platelet activation in the early phases of UA, potentially participating in the pathogenesis of acute coronary syndromes.
Lupia
Enrico
E
Azienda Ospedaliera San Giovanni Battista-Molinette, Turin, Italy.
Bosco
Ornella
O
Bergerone
Serena
S
Dondi
Anna Erna
AE
Goffi
Alberto
A
Oliaro
Elena
E
Cordero
Marco
M
Del Sorbo
Lorenzo
L
Trevi
Giampaolo
G
Montrucchio
Giuseppe
G
D000368:Aged; D000789:Angina, Unstable / Q000097:blood*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009000:Monocytes; D015539:Platelet Activation; D053628:Receptors, Thrombopoietin / Q000097:blood; D011994:Recombinant Proteins / Q000494:pharmacology; D013926:Thrombopoietin / Q000097:blood* / Q000494:pharmacology
D053628:Receptors, Thrombopoietin; D011994:Recombinant Proteins; C082218:MPL protein, human; D013926:Thrombopoietin