Ohgushi M, Kugiyama K, Fukunaga K, Murohara T, Sugiyama S, Miyamoto E, Yasue H
Division of Cardiology, Kumamoto University School of Medicine, Japan.
Arterioscler Thromb. 1993 Oct;13(10):1525-32. doi: 10.1161/01.atv.13.10.1525.
The mechanism(s) of inhibition of endothelium-dependent relaxation (EDR) by oxidized low-density lipoprotein (Ox-LDL) was examined in isolated porcine coronary arteries and rabbit aortas. Incubation with Ox-LDL but not native LDL caused the inhibition of thrombin- or acetylcholine-induced EDR, whereas A23187-induced EDR was preserved after incubation with Ox-LDL. Lysophosphatidylcholine (lysoPC), which was abundant in Ox-LDL and was found to be transferred from Ox-LDL to endothelial cells, also caused the inhibition of EDR in response to thrombin or acetylcholine but not to A23187. Ox-LDL depleted of lysoPC, which was prepared by phospholipase B, failed to inhibit the vasorelaxation. Coincubation with staurosporine or calphostin C, potent inhibitors of protein kinase C, attenuated the EDR inhibition by Ox-LDL or lysoPC. Phorbol 12-myristate 13-acetate, a specific protein kinase C activator, caused the EDR inhibition, and its effect was attenuated by staurosporine or calphostin C. Furthermore, lysoPC was capable of activating protein kinase C purified from cultured porcine endothelial cells. In conclusion, protein kinase C activation plays a role in the inhibition of surface receptor-mediated EDR by Ox-LDL, and lysoPC transferred from Ox-LDL to endothelial cells may be involved in the activation of protein kinase C.
在离体猪冠状动脉和兔主动脉中研究了氧化型低密度脂蛋白（Ox-LDL）抑制内皮依赖性舒张（EDR）的机制。与Ox-LDL而非天然LDL孵育会导致凝血酶或乙酰胆碱诱导的EDR受到抑制，而与Ox-LDL孵育后A23187诱导的EDR仍得以保留。溶血磷脂酰胆碱（lysoPC）在Ox-LDL中含量丰富，且发现其可从Ox-LDL转移至内皮细胞，它也会导致对凝血酶或乙酰胆碱而非A23187的EDR抑制。用磷脂酶B制备的不含lysoPC的Ox-LDL无法抑制血管舒张。与蛋白激酶C的强效抑制剂星形孢菌素或钙泊三醇C共同孵育可减弱Ox-LDL或lysoPC对EDR的抑制作用。佛波酯12-肉豆蔻酸酯13-乙酸酯，一种特异性蛋白激酶C激活剂，可导致EDR抑制，其作用可被星形孢菌素或钙泊三醇C减弱。此外，lysoPC能够激活从培养的猪内皮细胞中纯化的蛋白激酶C。总之，蛋白激酶C激活在Ox-LDL抑制表面受体介导的EDR中起作用，且从Ox-LDL转移至内皮细胞的lysoPC可能参与蛋白激酶C的激活。
