Lysophosphatidylcholine in oxidized low-density lipoprotein increases endothelial susceptibility to polymorphonuclear leukocyte-induced endothelial dysfunction in porcine coronary arteries. Role of protein kinase C.
We have shown that transferred lysophosphatidylcholine (lysoPC) from oxidized low-density lipoprotein (Ox-LDL) to endothelial surface membrane activates protein kinase C (PKC) in endothelial cells, suggesting that Ox-LDL could alter endothelial functions through PKC activation. The purposes of the present study were to examine whether the endothelial susceptibility to polymorphonuclear leukocytes (PMNs) may be altered in Ox-LDL-treated coronary arteries, which have properties closely resembling those observed in atherosclerotic arteries, and to determine the mechanism(s) by which Ox-LDL may affect the endothelial susceptibility to PMNs. Isolated porcine coronary arteries were cannulated and perfused with oxygenated culture medium with or without LDLs or lipids at a constant flow (37 degrees C, pH 7.4). The treatment of porcine coronary arteries with Ox-LDL increased endothelial adhesiveness to PMNs and augmented PMN-induced impairment of endothelium-dependent arterial relaxation (EDR). Furthermore, Ox-LDL stimulated the expression of intercellular adhesion molecule-1 (ICAM-1) in the porcine coronary arterial endothelium. These effects of Ox-LDL were not mediated by the scavenger-receptor-mediated process but were attributed to lysoPC in Ox-LDL. Blocking of the PMN adherence to endothelium by using anti-CD18 monoclonal antibody abolished the PMN-induced impairment of EDR. Coincubation with staurosporine or calphostin C, inhibitors of PKC, during treatment of the arteries with Ox-LDL or lysoPC attenuated the augmentative effects of Ox-LDL and lysoPC on endothelial ICAM-1 expression, endothelial adhesiveness to PMNs, and PMN-induced EDR impairment. Treatment of the arteries with phorbol 12-myristate 13-acetate, a potent stimulator of PKC, induced ICAM-1 expression and enhanced the endothelial adhesiveness to PMNs and PMN-induced EDR impairment, mimicking the effects of Ox-LDL. These results suggest that lysoPC in Ox-LDL induces endothelial ICAM-1 expression, which facilitates PMN adherence to endothelium and the subsequent augmentation of PMN-induced EDR impairment. PKC activation in endothelial cells by lysoPC in Ox-LDL may at least in part be involved in these effects of Ox-LDL. LysoPC in Ox-LDL increases endothelial susceptibility to PMN-induced endothelial dysfunction.
Sugiyama
S
S
Division of Cardiology, Kumamoto University School of Medicine, Japan.
Kugiyama
K
K
Ohgushi
M
M
Fujimoto
K
K
Yasue
H
H
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000032:analysis; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D008565:Membrane Proteins; D009504:Neutrophils / Q000502:physiology*; D010084:Oxidation-Reduction; D011493:Protein Kinase C / Q000032:analysis / Q000502:physiology*; D011971:Receptors, Immunologic / Q000502:physiology; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D013552:Swine; D014664:Vasodilation / Q000187:drug effects
D015815:Cell Adhesion Molecules; D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D011493:Protein Kinase C