Platelet arachidonic acid metabolism in patients with cardiovascular disorders

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.