Oxidized low-density lipoprotein inhibits endothelium-dependent vasodilation by an antioxidant-sensitive, lysophosphatidylcholine-independent mechanism
Oxidized low-density lipoprotein inhibits endothelium-dependent vasodilation by an antioxidant-sensitive, lysophosphatidylcholine-independent mechanism
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DOI：
10.1097/00005344-200306000-00005
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发表时间：
2003-06-01
影响因子：
3
通讯作者：
Steinbrecher, UP
中科院分区：
文献类型：
--
作者：
Chan, H;Lougheed, F;Steinbrecher, UP
先前的研究表明，氧化低密度脂蛋白（LDL）会损害内皮功能，这可以通过体内给予维生素E来克服。然而，目前还不清楚氧化LDL的这种作用是否是由于溶血磷脂酰胆碱或氧化LDL的其他成分，也不确定维生素E的保护作用是否与其抗氧化作用有关。本研究的目的是确定有多少广泛氧化的LDL对内皮依赖性舒张（EDR）的影响实际上是由于溶血磷脂酰胆碱，以确定氧化LDL的影响是否涉及氧化应激内皮，如果是这样，以确定这是否可以通过氧自由基清除剂或抗氧化剂阻断。内皮功能进行了评估，通过测量血管舒张预收缩大鼠肠系膜动脉环对乙酰胆碱。在存在100 μ g/mL氧化LDL的情况下，对于相同程度的血管舒张素，需要25倍更高浓度的乙酰胆碱。类似浓度的天然LDL或乙酰LDL没有影响，但100 μ g/mL磷脂酶A2处理的LDL或20 μ M溶血磷脂酰胆碱产生类似的EDR抑制。从氧化LDL中去除90%以上的溶血磷脂酰胆碱并不影响其抑制EDR的能力，也不影响用硼氢化物处理氧化LDL。氧化LDL的这种作用被阻断预孵育的动脉环与维生素E，普罗布考，或BO-653（一种有效的亲脂性抗氧化剂），但不是由超氧化物歧化酶。相反，溶血磷脂酰胆碱对EDR的抑制作用不受抗氧化剂的影响。Calphostin C可阻止氧化LDL和溶血磷脂酰胆碱对EDR的抑制作用。这些研究表明，氧化LDL对EDR的影响至少部分独立于溶血磷脂酰胆碱、脂质过氧化物和超氧化物释放，但似乎涉及细胞内氧化应激和蛋白激酶C激活。
Previous studies have shown that oxidized low-density lipoprotein (LDL) can impair endothelial function and that this can be overcome in vivo by administration of vitamin E. However, it is unclear whether this effect of oxidized LDL is due to lysophosphatidylcholine or other components of oxidized LDL, and it is also uncertain if the protective effect of vitamin E is related to its antioxidant action. The objectives of the current study were to define how much of the effect of extensively oxidized LDL on endothelium-dependent relaxation (EDR) was in fact due to lysophosphatidylcholine, to determine if the effect of oxidized LDL involved oxidant stress to the endothelium, and, if so, to ascertain if this could be blocked by oxyradical scavengers or antioxidants. Endothelial function was assessed by measuring vasodilation in preconstricted rat mesenteric artery rings in response to acetylcholine. In the presence of 100 mug/mL oxidized LDL, 25-fold higher concentrations of acetylcholine were required for the same degree of vasorclaxation. Similar concentrations of native LDL or acetyl LDL had no effect, but 100 mug/mL phospholipase A2-treated LDL or 20 muM lysophosphatidylcholine produced a similar inhibition of EDR. Removal of more than 90% of lysophosphatidylcholine from oxidized LDL did not affect its ability to inhibit EDR, nor did treatment of oxidized LDL with borohydride. This effect of oxidized LDL was blocked by preincubation of arterial rings with vitamin E, probucol, or BO-653 (a potent lipophilic antioxidant), but not by superoxide dismutase. In contrast, the inhibition of EDR by lysophosphatidylcholine was unaffected by antioxidants. Calphostin C prevented the inhibition of EDR by oxidized LDL and lysophosphatidylcholine. These studies demonstrate that at least part of the effect of oxidized LDL on EDR is independent of lysophosphatidylcholine, lipid peroxides, and superoxide release but appears to involve intracellular oxidative stress and protein kinase C activation.