Vascular remodeling in Nox1/NADPH oxidase deficient mice

2006 Fiscal Year Final Research Report Summary

• Project/Area Number: 17590225
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: YABE Chihiro (西村 千尋) Kyoto Prefectural University of Medicine, Graduate School of Medicine, Professor, 医学研究科, 教授 (70150571)
• Co-Investigator(Kenkyū-buntansha): OKIGAKI Mitsuhiko Kyoto Prefectural University of Medicine, Graduate School of Medicine, Instructor, 医学研究科, 助手 (10333197) ; IWATA Kazumi Kyoto Prefectural University of Medicine, Graduate School of Medicine, Instructor, 医学研究科, 助手 (60305571)
• Project Period (FY): 2005 – 2006
• Keywords: Genetically modified mice / Reactive oxygen species / Cardiovascular system

Research Abstract

NADPH oxidase is a superoxide-generating enzyme composed of multiple subunits including a membrane-spanning catalytic subunit, Nox. A newly identified isoform of Nox, Nox1 has been implicated in the development of angiotensin II-induced hypertension. We recently observed that the expression of the Nox1 gene is upregulated in the aorta of mice injected with lipopolysaccharide (LPS). Since chronic exposure to endotoxin (such as in periodontal disease) is a risk factor of atherosclerosis, we examined whether increased activity of Nox1 /NADPH oxidase is associated with the development of vascular remodeling using genetically modified mice.
Nox1-deficient mice (KO) were crossed with apoE-deficient mice to generate double knockout (DKO) mice. DKO mice maintained on high fat diet for 4 to 24 weeks were sacrificed, and isolated aortas were subjected to Oil red O staining. No difference was observed in the area of atherosclerotic region between DKO and KO treated with or without angiotensin II (500ng/kg/min). Accordingly, the absence of Nox1 /NADPH oxidase did not affect the development of atherosclerosis in mice.
Following LPS injection, the expression of Nox1 mRNA was markedly elevated in many organs. We are currently investigating the role of Nox1 /NADPH oxidase in the pathogenesis of endotoxin-induced lethal shock.