INCREASED PROSTACYCLIN BIOSYNTHESIS IN PATIENTS WITH SEVERE ATHEROSCLEROSIS AND PLATELET ACTIVATION
INCREASED PROSTACYCLIN BIOSYNTHESIS IN PATIENTS WITH SEVERE ATHEROSCLEROSIS AND PLATELET ACTIVATION
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DOI：
10.1056/nejm198404263101701
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发表时间：
1984-01-01
影响因子：
158.5
通讯作者：
BRASH, AR
中科院分区：
文献类型：
--
作者：
FITZGERALD, GA;SMITH, B;BRASH, AR
前列环素是一种有效的血管扩张剂和血小板抑制剂，由血管内皮细胞产生。生理条件下前列环素的内源性产生极低，远低于血管组织响应体外刺激产生这种物质的能力。这可能反映了前列腺素产生的刺激频率或强度较低。如果前列环素确实作为内源性血小板抑制剂，那么在血小板-血管相互作用可能增加的临床环境中，前列环素的产生量应该更大。为了验证这一假设，前列环素的生物合成在严重动脉粥样硬化和体内血小板活化证据的患者中进行了检查。2，3-二去甲-6-酮-前列腺素F1 α的排泄，尿前列环素主要代谢物，在9名严重动脉粥样硬化和血小板活化证据患者中（251-1859 pg/mg肌酐）显著高于54名健康志愿者（45-219 pg/mg肌酐; P < 0.001）。这种差异代表了生物合成而不是代谢的改变，因为两组中输注的前列环素转化为地诺代谢物的分数相同。前列环素的产生在健康人中可能很低，因为几乎没有刺激其产生，但在患有严重动脉粥样硬化的患者中由于血小板与内皮相互作用或其他血管损伤而增强。前列环素可能作为血小板-血管相互作用的局部调节剂发挥作用。
Prostacyclin is a potent vasodilator and platelet inhibitor produced by vascular endothelium. Endogenous production of prostacyclin under physiologic conditions is extremely low, far below the capacity of vascular tissue to generate this substance in response to stimulation in vitro. This may reflect a low frequency or intensity of stimulation of prostacylin production. If prostacyclin does act as an endogenous platelet-inhibitory agent, it should be produced in greater amounts in a clinical setting in which platelet-vascular interactions are likely to be increased. To test this hypothesis, prostacyclin biosynthesis was examined in patients with severe atherosclerosis and evidence of platelet activation in vivo. Excretion of 2,3-dinor-6-keto-prostaglandin F1.alpha., a major urinary prostacyclin metabolite, was significantly higher in 9 patients with severe atherosclerosis and evidence of platelet activation (251-1859 pg/mg of creatinine) than in 54 healthy volunteers (45-219 pg/mg of creatinine; P < 0.001). This difference represented an alteration in biosynthesis rather than in metabolism, since the fractional conversion of infused prostacyclin to the dinor metabolite was identical in both groups. Prostacyclin production may be low in healthy persons because there is almost no stimulus for its production, but enhanced in patients with severe atherosclerosis as a consequence of platelet interactions with endothelium or other vascular insults. Prostacyclin may have a role as a local regulator of platelet-vascular interactions.