Role of Lipocalin-Type Prostaglandin D Synthase on Coronary Atherosclerosis and Vascular Function

脂钙素型前列腺素D合成酶（L-PGDS）催化前列腺素d2 （PGD2）的生物合成，具有抗凝血、血管舒张和炎症介质的作用。我们假设L-PGDS对冠状血管痉挛的发生有临床影响。因此，我们检测了96例胸痛和冠状动脉造影正常的患者血清L-PGDS水平、冠状动脉大血管和小血管舒缩功能及其关系。方法：将乙酰胆碱（ACh）按递增剂量（3、10、30、100 μg/min）注入左冠状动脉，采用定量血管造影和多普勒导丝检查分析左冠状动脉前降支（LAD）直径和血流变化。采用ELISA法测定血管造影前血清L-PGDS水平。结果：所有冠状血管痉挛性心绞痛（CSA）患者输注乙酰胆碱均可引起LAD冠状血管痉挛，而胸痛（CP）综合征患者均无此反应。乙酰胆碱在CP组引起边缘血管收缩，但在CSA组引起LAD动脉的剂量依赖性收缩。0.25 mg硝酸甘油引起的冠状动脉血管扩张或12 mg罂粟碱引起的冠状动脉血流增加在两组之间没有差异。除吸烟频率外，CP组和CSA组的基线临床特征无显著差异。CSA组血清L-PGDS水平显著高于CP组。校正吸烟状况也产生了类似的结果。乙酰胆碱（3、10、30 μg/min）作用下LAD血管舒缩程度与血清L-PGDS水平呈显著负相关。血清L-PGDS水平与硝酸甘油或罂粟碱引起的冠状动脉血管舒张无关。结论：L-PGDS可能是CSA患者冠状动脉血管反应性的预测因子。

Lipocalin-type prostaglandin D synthase (L-PGDS) catalyzes the biosynthesis of prostaglandin D_2 (PGD2), which acts as an anticoagulant, vasodilaor, and inflammatory mediator. We hypothesized that L-PGDS has clinical impact on the genesis of coronary vasospasm. Thus, we examined serum L-PGDS levels, coronary macro-and microvasomotor function, and their relationship in 96 patients with chest pain and angiographically normal coronary arteries. Methods : Acetylcholine (ACh) at increasing doses (3, 10, 30, 100 μg/min) was infused into the left coronary artery, and the diameter and blood flow of the left anterior descending coronary artery (LAD) were analyzed by quantitative angiography and Doppler guide wire examination. The serum L-PGDS level prior to angiography was determined by the ELISA method. Results : Infusion of ACh induced coronary vasospasm of the LAD in all patients with coronary vasospastic angina (CSA), but in none of the patients with chest pain (CP) syndrome. ACh caused marginal vasoconstriction in the CP group, but produced dose-dependent constrictions of LAD arteries in the CSA group. Coronary vasodilations induced by 0.25 mg of nitoroglycerin or increases in coronary blood flow induced by 12 mg of papaverine did not differ between the two groups. There were no significant differences in baseline clinical characteristics between the CP and CSA groups, except for the frequency of smoking. Serum L-PGDS levels in the CSA group were significantly higher than those in the CP group. Correction of smoking status yielded similar results. Significant negative correlations were observed between the degrees of LAD vasomotion in response to ACh (3, 10, 30 μg/min) and serum L-PGDS levels. Serum L-PGDS levels did not correlate with coronary vasomotions induced by nitoroglycerin or papaverine.Conclusion : L-PGDS may be a predictor of coronary vascular reactivity in patients with CSA.