Protein Kinase C Inhibitors Prevent Impairment of Endothelium‐Dependent Relaxation by Oxidatively Modified LDL
作者:
Masamichi Ohgushi,
Kiyotaka Kugiyama,
Kohji Fukunaga,
Toyoaki Murohara,
Seigo Sugiyama,
Eishichi Miyamoto,
Hirofumi Yasue,
期刊:
Arteriosclerosis and Thrombosis: A Journal of Vascular Biology
(OVID Available online 1993)
卷期:
Volume 13,
issue 10
页码: 1525-1532
ISSN:1049-8834
年代: 1993
出版商: OVID
关键词: protein kinase C;staurosporine;calphostin C;lysophosphatidylcholine oxidized LDL
数据来源: OVID
摘要:
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 thrombinor 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. Colncubatlon 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.
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