3 research outputs found
233 Loss of IRF Signaling Contributes to the Development of Helicobacter Associated Gastric Carcinogenesis In Vivo
Arterial wall hypertrophy is ameliorated by α2-adrenergic receptor antagonist or aliskiren in kidneys of angiotensinogen-knockout mice
Requirement of Apelin-Apelin Receptor System for Oxidative Stress-Linked Atherosclerosis
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 α-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