There is increasing evidence that prostaglandins (PG) and thromboxane (Tx) play a major role in the pathogenesis of coronary artery disease. The regulation of arachidonic acid (AA) metabolism through cyclooxygenase (COx) pathway and the AA-dependent Ca2+ influx were investigated in platelets from 10 patients with unstable angina and 10 controls. The activation of the hexose monophosphate shunt (HMS), a sensitive index of the flux through the PGG2 to PGH2 step of the COx pathway, in response to AA was significantly enhanced in platelets from patients. AA-induced malonyldialdehyde (MDA) production as well as AA-evoked Ca2+ flux and glutathione-dependent peroxidase activity resulted significantly increased. Moreover, platelet sensitivity to prostacyclin (PGI2), measured as inhibition of Ca2+ flux, was highly decreased. Thus far, evidence is presented for intrinsic platelet hyperactivity (at the PG-peroxidase reaction of the COx pathway) in patients with unstable angina: the resulting increase in PGH2 and TxA2 synthesis, alone or in combination with decreased PGI2 sensitivity, may account for a facilitated thrombus formation.
Platelet arachidonic acid metabolism in patients with cardiovascular disorders.
GHIGO, Dario Antonio;BUSSOLINO, Federico;ORZAN, Fulvio;BOSIA, Amalia
1988-01-01
Abstract
There is increasing evidence that prostaglandins (PG) and thromboxane (Tx) play a major role in the pathogenesis of coronary artery disease. The regulation of arachidonic acid (AA) metabolism through cyclooxygenase (COx) pathway and the AA-dependent Ca2+ influx were investigated in platelets from 10 patients with unstable angina and 10 controls. The activation of the hexose monophosphate shunt (HMS), a sensitive index of the flux through the PGG2 to PGH2 step of the COx pathway, in response to AA was significantly enhanced in platelets from patients. AA-induced malonyldialdehyde (MDA) production as well as AA-evoked Ca2+ flux and glutathione-dependent peroxidase activity resulted significantly increased. Moreover, platelet sensitivity to prostacyclin (PGI2), measured as inhibition of Ca2+ flux, was highly decreased. Thus far, evidence is presented for intrinsic platelet hyperactivity (at the PG-peroxidase reaction of the COx pathway) in patients with unstable angina: the resulting increase in PGH2 and TxA2 synthesis, alone or in combination with decreased PGI2 sensitivity, may account for a facilitated thrombus formation.
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