Ghigo D, Treves S, Bussolino F, Libero L, Orzan F, Bazzan M, Pannocchia A, Tamponi G, Bosia A
Dipartimento di Genetica, Biologia e Chimica Medica, Universita' di Torino, Italy.
Biomed Biochim Acta. 1988;47(10-11):S299-302.
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.
越来越多的证据表明，前列腺素（PG）和血栓素（Tx）在冠状动脉疾病的发病机制中起主要作用。在10例不稳定型心绞痛患者和10例对照者的血小板中，研究了通过环氧合酶（COx）途径对花生四烯酸（AA）代谢的调节以及AA依赖性Ca2+内流。患者血小板中，作为COx途径从PGG2到PGH2步骤通量的敏感指标，磷酸己糖旁路（HMS）对AA的激活显著增强。AA诱导的丙二醛（MDA）生成以及AA诱发的Ca2+通量和谷胱甘肽依赖性过氧化物酶活性均显著增加。此外，以抑制Ca2+通量衡量的血小板对前列环素（PGI2）的敏感性大幅降低。迄今为止，有证据表明不稳定型心绞痛患者存在血小板内在活性亢进（在COx途径的PG-过氧化物酶反应中）：由此导致的PGH2和TxA2合成增加，单独或与PGI2敏感性降低相结合，可能导致血栓形成加速。
