title: Requirement of apelin-apelin receptor system for oxidative stress-linked atherosclerosis.
abstract: The recently identified endogenous peptide apelin and its specific apelin receptor (APJ) are currently being considered as potential regulators in vascular tissue. Previously, we reported apelin mediates phosphorylation of myosin light chain and elicits vasoconstriction in vascular smooth muscle. In this study, physiological roles of the apelin-APJ system were investigated on atherosclerosis. In APJ and apolipoprotein E double-knockout (APJ(-/-)ApoE(-/-)) mice fed a high-cholesterol diet, atherosclerotic lesions were dramatically reduced when compared with APJ(+/+) ApoE(-/-) mice, in the absence of an effect of cholesterol levels. Immunohistochemical detection of smooth muscle cells, using a smooth muscle alpha-actin antibody, showed greatly reduced staining for these cells in lesions of APJ(-/-)ApoE(-/-) mice fed a high-cholesterol diet. Vascular production of superoxide radicals and the expression of nicotinamide-adenine dinucleotide phosphate oxidase subunits were decreased in APJ(-/-)ApoE(-/-) mice compared with APJ(+/+)ApoE(-/-) mice fed a standard normal diet. In vascular smooth muscle cells, apelin induced nicotinamide-adenine dinucleotide phosphate oxidase subunit expression. Apelin also induced vascular smooth muscle cell proliferation, which was inhibited by superoxide dismutase or diphenylene iodonium. The apelin-APJ system is a mediator of oxidative stress in vascular tissue, and thus we propose it to be a critical factor in atherogenesis under high-cholesterol dietary conditions. APJ deficiency is preventative against oxidative stress-linked atherosclerosis.
authors: Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine and School of Medicine, Kanazawa-ku, Yokohama, Japan.
authors: Tatsuo
authors: T
authors: Hashimoto
authors: Minoru
authors: M
authors: Kihara
authors: Nozomi
authors: N
authors: Imai
authors: Shin-Ichiro
authors: S
authors: Yoshida
authors: Hiroaki
authors: H
authors: Shimoyamada
authors: Hiroaki
authors: H
authors: Yasuzaki
authors: Junji
authors: J
authors: Ishida
authors: Yoshiyuki
authors: Y
authors: Toya
authors: Yoshihiro
authors: Y
authors: Kiuchi
authors: Nobuhito
authors: N
authors: Hirawa
authors: Kouichi
authors: K
authors: Tamura
authors: Takuya
authors: T
authors: Yazawa
authors: Hitoshi
authors: H
authors: Kitamura
authors: Akiyoshi
authors: A
authors: Fukamizu
authors: Satoshi
authors: S
authors: Umemura
mesh_terms: D054392:Adipokines; D000818:Animals; D000073861:Apelin; D000075244:Apelin Receptors; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology*; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D049109:Cell Proliferation; D004036:Diet, Atherogenic; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*
chemical_list: D054392:Adipokines; D000073861:Apelin; D000075244:Apelin Receptors; C402826:Apln protein, mouse; C491285:Aplnr protein, mouse; D001057:Apolipoproteins E; D002352:Carrier Proteins; D036341:Intercellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled; D019255:NADPH Oxidases