Cyclic Phosphatidic Acid inhibits the Secretion of Vascular Endothelial Growth Factor from Diabetic Human Coronary Artery Endothelial Cells through Peroxisome Proliferator-activated Receptor Gamma
Cyclic Phosphatidic Acid inhibits the Secretion of Vascular Endothelial Growth Factor from Diabetic Human Coronary Artery Endothelial Cells through Peroxisome Proliferator-activated Receptor Gamma
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环磷脂酸通过过氧化物酶体增殖物激活受体γ抑制糖尿病人冠状动脉内皮细胞分泌血管内皮生长因子
DOI：
10.1016/j.mce.2015.05.021
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发表时间：
2015
影响因子：
4.1
通讯作者：
and Kimiko Murakami-Murofushi
中科院分区：
文献类型：
--
作者：
Tamotsu Tsukahara;Ryoko Tsukahara;Hisao Haniu Yoshikazu Matsuda;and Kimiko Murakami-Murofushi
动脉粥样硬化是一种以斑块形成为特征的疾病，并导致动脉被脂肪物质如胆固醇堵塞的潜在严重状况。越来越多的证据表明，动脉粥样硬化在2型糖尿病中加速。近年来的研究发现，动脉粥样硬化病变组织中存在高水平的烷基甘油磷酸盐（AGP）。轻度氧化的低密度脂蛋白（LDL）中存在这种磷脂可能与动脉粥样硬化形成有关。据报道，过氧化物酶体增殖物激活受体γ的激活在动脉粥样硬化的发展中起着关键作用。我们的前期研究结果表明，环磷脂酸（cPA）是一种生物活性脂质，通过抑制过氧化物酶体增殖物激活受体γ（PPARγ）的活化，有效地抑制新生内膜的形成。但具体机制尚不清楚。本研究通过观察糖尿病患者冠状动脉内皮细胞（human coronary artery endothelial cells from diabetes patients，D-HCAECs）的增殖、迁移和VEGF的分泌，探讨cPA-PPARγ轴在糖尿病患者冠状动脉内皮细胞中的作用机制。AGP可诱导D-HCAECs的生长和迁移，cPA可抑制AGP诱导的D-HCAECs的生长和迁移。此外，AGP增加D-HCAECs的VEGF分泌，cPA减弱了该事件。总之，这些结果表明，cPA抑制VEGF刺激的生长和迁移的D-HCAEC。这些发现可能对PPARγ和VEGF在与糖尿病和动脉粥样硬化相关的血管过程中的调节作用具有重要意义。
Atherosclerosis is a disease characterized by building up plaques formation and leads to a potentially serious condition in which arteries are clogged by fatty substances such as cholesterol. Increasing evidence suggests that atherosclerosis is accelerated in type 2 diabetes. Recent study reported that high level of alkyl glycerophosphate (AGP) was accumulated in atherosclerotic lesions. The presence of this phospholipid in mildly oxidized low-density lipoprotein (LDL) is likely to be involved in atherogenesis. It has been reported that the activation of peroxisome proliferator-activated receptor gamma plays a key role in developing atherosclerosis. Our previous result indicates that cyclic phosphatidic acid (cPA), one of bioactive lipids, potently suppresses neointima formation by inhibiting the activation of peroxisome proliferator-activated receptor gamma (PPARγ). However, the detailed mechanism is still unclear. In this study, to elucidate the mechanism of the cPA-PPARγ axis in the coronary artery endothelium, especially in patients with type 2 diabetes, we investigated the proliferation, migration, and secretion of VEGF in human coronary artery endothelial cells from diabetes patients (D-HCAECs). AGP induced cell growth and migration; however, cPA suppressed the AGP-elicited growth and migration in D-HCAECs. Moreover, AGP increased VEGF secretion from D-HCAECs, and this event was attenuated by cPA. Taken together, these results suggest that cPA suppresses VEGF-stimulated growth and migration in D-HCAECs. These findings could be important for regulatory roles of PPARγ and VEGF in the vascular processes associated with diabetes and atherosclerosis.