Lysophosphatidic acid causes endothelial dysfunction in porcine coronary arteries and human coronary artery endothelial cells.
Lysophosphatidic acid causes endothelial dysfunction in porcine coronary arteries and human coronary artery endothelial cells.
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DOI：
10.1016/j.atherosclerosis.2012.02.010
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发表时间：
2012-05
期刊：
影响因子：
5.3
通讯作者：
Yao Q
中科院分区：
文献类型：
--
作者：
Chen C;Ochoa LN;Kagan A;Chai H;Liang Z;Lin PH;Yao Q
本研究旨在探讨溶血磷脂酸（LPA）对猪冠状动脉和人冠状动脉内皮细胞（HCAECs）内皮功能和分子变化的影响。血管环和HCAEC用临床相关浓度的LPA处理不同时间。血管反应性研究与肌张力系统。与对照组相比，LPA（10和50 µM）处理血管环显著降低了缓激肽（10−5 M）引起的内皮依赖性血管舒张反应，分别降低了32%和49%（P<0.05）。LPA降低血管环内皮型一氧化氮合酶（eNOS）mRNA和免疫反应性水平。在HCAEC中，LPA降低eNOS mRNA、磷酸化eNOS和总eNOS蛋白水平。此外，超氧阴离子水平在LPA处理的血管环和HCAECs显着增加，分别通过lucegenin增强化学发光法和二氢乙锭染色。线粒体膜电位和ATP含量明显降低。活性氧产生酶NOX4和p40phox的mRNA水平增加，而内源性抗氧化酶超氧化物歧化酶1在响应LPA处理的HCAECs下降。此外，外源性抗氧化分子硒蛋氨酸（SeMet）有效地扭转了这些LPA诱导的猪冠状动脉和HCAEC的影响。LPA通过与猪冠状动脉和HCAEC中eNOS表达降低和氧化应激增加相关的机制引起内皮功能障碍。
The objective of this study was to determine the effects of lysophosphatidic acid (LPA) on endothelial functions and molecular alternations in both porcine coronary arteries and human coronary artery endothelial cells (HCAECs). The vessel rings and HCAECs were treated with clinically relevant concentrations of LPA for different times. Vasomotor reactivity was studied with a myograph tension system. LPA (10 and 50 µM) treatment for the vessel rings significantly reduced endothelium-dependent vasorelaxation in response to bradykinin (10−5 M) by 32% and 49%, respectively, compared with the control (P<0.05). LPA decreased endothelial nitric oxide synthase (eNOS) mRNA and immunoreactivity levels in the vessel rings. In HCAECs, LPA reduced eNOS mRNA, phospho-eNOS and total eNOS protein levels. In addition, superoxide anion levels in LPA-treated vessel rings and HCAECs were significantly increased by lucegenin-enhanced chemiluminescence assay and dihydroethidium staining, respectively. Mitochondrial membrane potential and ATP content in LPA-treated HCAECs were substantially decreased. The mRNA levels of reactive oxygen species generating enzymes NOX4 and p40phox were increased, while endogenous antioxidant enzyme superoxide dismutase 1 was decreased in response to LPA treatment in HCAECs. Furthermore, exogenous antioxidant molecule selenomethionine (SeMet) effectively reversed these LPA-induced effects in both porcine coronary arteries and HCAECs. LPA causes endothelial dysfunction by a mechanism associated with decreased eNOS expression and increased oxidative stress in porcine coronary arteries and HCAECs.
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