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

Lipocalin型前列腺素D合成酶(L-PGDS)催化前列腺素D_2(PGD_2)的生物合成，前列腺素D_2具有抗凝、血管扩张和炎症介质的作用。我们推测L-前列腺素DS在冠状动脉血管痉挛的发生中具有临床意义。因此，我们检测了96例胸痛和冠状动脉造影术正常的患者的血清L-前列腺素DS水平、冠脉大血管和微血管运动功能及其相互关系。方法：左冠状动脉内注入不同剂量(3、10、30、100min)的乙酰胆碱(ACh)，定量冠状动脉造影术和多普勒导丝检测左冠状动脉前降支(LAD)的内径和血流量。采用双抗体夹心ELISA法测定造影前血清L-前列腺素DS水平。结果：所有冠脉血管痉挛心绞痛(CSA)患者均可出现ACh诱发的LAD血管痉挛，但胸痛(CP)综合征患者无一例出现LAD痉挛。ACh在CP组引起边缘血管收缩，而在CsA组引起剂量依赖性的LAD动脉收缩。0.25 mg硝酸甘油引起的冠状动脉扩张或12 mg罂粟碱引起的冠状动脉血流量增加在两组之间没有差异。除吸烟频率外，CP组和CsA组的基线临床特征没有显著差异。CsA组血清L-PGDS水平明显高于CP组。对吸烟状况的纠正也产生了类似的结果。ACh(3、10、30ming/μ)引起的LAD血管运动程度与血清L-前列腺素DS水平呈显著负相关。血清L-PGDS水平与硝酸甘油和罂粟碱诱导的冠状动脉血管运动无相关性。结论：L-PGDS可能是CsA患者冠状动脉反应性的预测指标。

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.