Graeber J E, Slott J H, Ulane R E, Schulman J D, Stuart M J
Pediatr Res. 1982 Jun;16(6):490-3. doi: 10.1203/00006450-198206000-00018.
Normal hemostasis depends in part on the balance achieved between proaggregatory and prothrombotic platelet thromboxane A2, measured as its stable end-product thromboxane B2 (TXB2), and vascular prostacyclin (PGI2), which inhibits platelet aggregation and is antithrombotic. Cystathionine-beta-synthase deficiency is characterized by a high frequency of thromboembolic disease. We therefore studied, in vitro, the effects of homocysteine and related compounds on platelet TXB2 and vascular PGI2 formation. In paired samples of platelet rich plasma, which had been preincubated with L-homocystine (1 mM), mean production of the two platelet cyclooxygenase products, TXB2 and 12-hydroxy-5, 8,10-heptadecatrienoic acid increased significantly from control levels [13.6% +/- 1.9 to 19.8% +/- 2.1 (P less than 0.02) TXB2 and 29.8% +/- 4.2 to 39.4% +/- 4.1 (P less than 0.01) HHT]. In the presence of D,L-homocysteine (1 mM), mean TXB2 and 12-hydroxy-5,8,10-heptadecatrienoic acid production was also significantly increased [12.7% +/- 1.5 to 16.9% +/- 1.5 (P less than 0.01) TXB2 and 27% +/- 4 to 31% +/- 4.1 (P less than 0.02) HHT]. Cystine, cysteine, or methionine (1 mM) did not have similar effects in this test system. Homocysteine and homocystine were without effect on the synthesis of vascular PGI2 by umbilical artery segments [control, 0.22 +/- 0.03 to 0.21 +/- 0.03 ng/mg with D,L-homocysteine and 0.20 +/- 0.04 control to 0.19 +/- 0.04 ng/mg with D,L-homocystine]. A homocyst(e)ine-induced increase in platelet thromboxane production in the absence of an increase in vascular prostacyclin, if present in vivo, may contribute to the vascular thromboses characteristic of human homocystinemias (homocystinurias).
正常止血部分取决于促聚集和促血栓形成的血小板血栓素A2（以其稳定终产物血栓素B2（TXB2）衡量）与血管前列环素（PGI2）之间达到的平衡，PGI2可抑制血小板聚集且具有抗血栓形成作用。胱硫醚-β-合酶缺乏症的特征是血栓栓塞性疾病的高发率。因此，我们在体外研究了同型半胱氨酸及相关化合物对血小板TXB2和血管PGI2形成的影响。在预先与L-同型胱氨酸（1 mM）孵育的富血小板血浆配对样本中，两种血小板环氧化酶产物TXB2和12-羟基-5,8,10-十七碳三烯酸的平均生成量较对照水平显著增加[TXB2从13.6%±1.9增至19.8%±2.1（P<0.02），12-羟基-5,8,10-十七碳三烯酸从29.8%±4.2增至39.4%±4.1（P<0.01）]。在存在D,L-同型半胱氨酸（1 mM）的情况下，TXB2和12-羟基-5,8,10-十七碳三烯酸的平均生成量也显著增加[TXB2从12.7%±1.5增至16.9%±1.5（P<0.01），12-羟基-5,8,10-十七碳三烯酸从27%±4增至31%±4.1（P<0.02）]。在该测试系统中，胱氨酸、半胱氨酸或蛋氨酸（1 mM）没有类似作用。同型半胱氨酸和同型胱氨酸对脐动脉段血管PGI2的合成没有影响[对照，D,L-同型半胱氨酸存在时从0.22±0.03降至0.21±0.03 ng/mg，D,L-同型胱氨酸存在时从0.20±0.04降至0.19±0.04 ng/mg]。如果在体内存在同型半胱氨酸诱导的血小板血栓素生成增加而血管前列环素不增加的情况，可能会导致人类同型半胱氨酸血症（同型胱氨酸尿症）特有的血管血栓形成。
