Complexes of apoA-1 with phosphatidylcholine suppress dysregulation of arterial tone by oxidized LDL.
The aim of this study was to determine whether apolipoprotein A-1 (apoA-1) may suppress the vasomotor dysregulation by oxidized low-density lipoprotein (ox-LDL), which is known to be an atherogenic lipoprotein. The isolated porcine coronary arterial rings and the cultured endothelial cells from the porcine coronary arteries were exposed to ox-LDL in the presence or absence of complexes of apoA-1 with dimyristoylphosphatidylcholine (DMPC/apoA-1), apoA-1 alone, or DMPC alone. DMPC/apoA-1 but not apoA-1 alone or DMPC alone was found to suppress both impairment of endothelium-dependent arterial relaxation and vasocontraction caused by ox-LDL in the isolated porcine coronary arterial rings suspended in organ chambers. DMPC/apoA-1 absorbed lysophosphatidylcholine (LPC) from ox-LDL and decreased the transfer of LPC from ox-LDL to the surface membrane of the cultured endothelial cells, but apoA-1 alone and DMPC alone had no effect. High-density lipoprotein exerted the protective actions mimicking those observed in DMPC/apoA-1. Thus DMPC/apoA-1 decreased the transfer of LPC from ox-LDL to surface membrane by absorbing LPC, leading to the suppression of ox-LDL-induced dysregulation of endothelium-dependent arterial tone. Therefore, apoA-1 appears to require formation of the complexes with phospholipids to prevent the endothelial dysfunction caused by ox-LDL.
Ota
Y
Y
Division of Cardiology, Kumamoto University School of Medicine, Japan.
Kugiyama
K
K
Sugiyama
S
S
Matsumura
T
T
Terano
T
T
Yasue
H
H
D000704:Analysis of Variance; D000818:Animals; D016632:Apolipoprotein A-I / Q000494:pharmacology*; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D004134:Dimyristoylphosphatidylcholine / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D008077:Lipoproteins, LDL / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009126:Muscle Relaxation / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D013552:Swine; D013917:Thrombin / Q000494:pharmacology
D016632:Apolipoprotein A-I; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D013917:Thrombin; D004134:Dimyristoylphosphatidylcholine