Impairment of endothelium-dependent arterial relaxation by lysolecithin in modified low-density lipoproteins.
Atherosclerosis in animals and humans is associated with an unresponsiveness of arteries and arterioles to endothelium-dependent vasodilators--agents acting on smooth muscle indirectly by stimulating the release from endothelial cells of a vasodilator principle (endothelium-derived relaxing factor). Altered vasomotor regulation in atherosclerosis could partly reflect an injurious action of abnormal lipoproteins on endothelium. Recently, 'cell-modified' or 'oxidized' low-density lipoprotein (EC-LDL) has received increasing attention because of its potential cytotoxic and atherogenic properties. We report here that arteries exposed to EC-LDL in vitro show an endothelium-dependent vasoregulatory impairment closely resembling that of atherosclerotic arteries. Our results indicate that transfer of lysolecithin from EC-LDL to endothelial membranes produces a selective unresponsiveness to receptor-regulated endothelium-dependent vasodilators.
Kugiyama
K
K
Department of Medicine, Baylor College of Medicine, Houston, Texas 77030.
Kerns
S A
SA
Morrisett
J D
JD
Roberts
R
R
Henry
P D
PD
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology*; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000502:physiology*; D066298:In Vitro Techniques; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D005996:Nitroglycerin / Q000494:pharmacology; D010084:Oxidation-Reduction; D010656:Phenylephrine / Q000494:pharmacology; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects*
D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D010656:Phenylephrine; D000001:Calcimycin; D005996:Nitroglycerin; D000109:Acetylcholine