Establishment of Prevention and Treatment for Development of Atherosclerosis by regulation of Lipocalin-Type Prostaglandin D Synthase

通过调节脂质运载蛋白型前列腺素D合酶来预防和治疗动脉粥样硬化的建立

• 批准号: 13670705
• 负责人: MATSUMOTO Tetsuya
• 金额: $ 2.3万
• 依托单位: Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670705/
• 关键词: Prostaglandin D2; Atherosclerosis; Coronary artery; Smooth muscle; Prostaglandin D_2

Lipocalin-type prostaglandin (PG) D synthase (L-PGDS), which is responsible for the biosynthesis of PGD2, has recently been found to be present in the atherosclerotic plaque of the human coronary artery and also to be detectable in human serum. L-PGDS is one of the enzymes that catalyze PGD2 synthesis, and so we speculate that PGD2 synthesis mediated by L-PGDS is related to pathogenesis of atherosclerosis. Considering the roles of L-PGDS in the pathophysiology of coronary artery disease, it is suggested that L-PGDS generation in the atherosclerotic plaques has an anti-atherogenic effect. Furthermore, we observed the immunoreactivity and mRNA expression of L-PGDS to confirm that L-PGDS was definitely localized and generated in atherosclerotic plaques, especially in these in the human and monkey coronary artery.The major findings are that serum L-PGDS level was elevated in patients with coronary artery disease and that the level increased in association with the number of affected vessels (Teruo inoue, Yutaka Eguchi, Tetsuya Matsumoto, Yoshihiro Urade et al. Lipocalin-type prostaglandin D synthase is a powerful biomarker for severity of coronary artery disease, submitted). The serum L-PGDS level may be suitable to evaluate the severity of coronary artery disease. It is concluded that the measurement of serum L-PGDS can be a strategy for screening of coronary artery disease prior to coronary angiography.

脂质运载蛋白型前列腺素 (PG) D 合酶 (L-PGDS) 负责 PGD2 的生物合成，最近发现其存在于人冠状动脉的动脉粥样硬化斑块中，并且在人血清中也可检测到。 L-PGDS是催化PGD2合成的酶之一，因此我们推测L-PGDS介导的PGD2合成与动脉粥样硬化的发病机制有关。考虑到 L-PGDS 在冠状动脉疾病病理生理学中的作用，表明动脉粥样硬化斑块中 L-PGDS 的生成具有抗动脉粥样硬化作用。此外，我们观察了 L-PGDS 的免疫反应性和 mRNA 表达，以证实 L-PGDS 明确定位于动脉粥样硬化斑块中并在动脉粥样硬化斑块中产生，特别是在人和猴冠状动脉中。主要发现是，冠状动脉疾病患者的血清 L-PGDS 水平升高，并且该水平升高与受影响的血管数量相关（Teruo inoue，Yutaka） 江口、松本哲也、浦手义宏等。脂质运载蛋白型前列腺素 D 合酶是冠状动脉疾病严重程度的强大生物标志物，已提交）。血清L-PGDS水平可能适合评估冠状动脉疾病的严重程度。结论是，血清 L-PGDS 的测量可以作为冠状动脉造影前筛查冠状动脉疾病的策略。

项目成果

Yokohama H, Matsumoto T, Horie H, Minai K, Kinoshita M.: "Coronary endothelium-dependent and independent vasomotor responses in patients with hypertrophic cardiomyopathy"Circ J.. 66(1). 30-34 (2002)

Yokohama H、Matsumoto T、Horie H、Minai K、Kinoshita M.：“肥厚型心肌病患者的冠状动脉内皮依赖性和独立血管舒缩反应”Circ J.. 66(1)。

Tsutamoto T et al.: "Relationship between tumor necrosis factor-alpha production and oxidative stress in the failing hearts of patients with dilated cardiomyopathy"J Am Coil Cardiol. 37. 2086-2092 (2001)

Tsutamoto T 等人：“扩张型心肌病患者衰竭心脏中肿瘤坏死因子-α 产生与氧化应激之间的关系”J Am Coil Cardiol。

Minai K et al.: "Bradykinin stimulates the release of tissue plasminogen activator in human coronary circulation : effects of angiotensin-converting enzyme inhibitors"J Am Coil Cardiol. 37. 1565-1570 (2001)

Minai K 等人：“缓激肽刺激人体冠状循环中组织纤溶酶原激活剂的释放：血管紧张素转换酶抑制剂的作用”J Am Coil Cardiol。

Teruo inoue, Yutaka Eguchi, Tetsuya Matsumoto, Yoshihiro Urade et al.: "Lipocalin-type prostaglandin D synthase is a powerful biomarker for severity of coronary artery disease"(in press).

Teruo inoue、Yutaka Eguchi、Tetsuya Matsumoto、Yoshihiro Urade 等人：“Lipocalin 型前列腺素 D 合酶是冠状动脉疾病严重程度的强大生物标志物”（出版中）。

Tsutamoto T, Wada A, Matsumoto T, Maeda K, Mabuchi N, Hayashi M, Tsutsui T, Ohnishi M, Sawaki M, Fujii M, Matsumoto T, Yamamoto T, Horie H, Sugimoto Y, Kinoshita M.: "Relationship between tumor necrosis factor-alpha production and oxidative stress in the

Tsutamoto T、Wada A、Matsumoto T、Maeda K、Mabuchi N、Hayashi M、Ttsutsui T、Ohnishi M、Sawaki M、Fujii M、Matsumoto T、Yamamoto T、Horie H、Sugimoto Y、Kinoshita M.：“肿瘤之间的关系