Decreased neointimal formation in Nox2-deficient mice reveals a direct role for NADPH oxidase in the response to arterial injury.
Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are produced, in part, from NADPH oxidase in response to host invasion and tissue injury. Defects in NADPH oxidase impair host defense; however, the role of ROS and RNS in the response to tissue injury is not known. We addressed this issue by subjecting leukocyte oxidase (Nox2)-deficient (Nox2-/-) mice to arterial injury. Femoral artery injury was associated with increased Nox2 expression, ROS/RNS production, and oxidative protein and lipid modification in wild-type mice. In Nox2-/- mice, RNS-mediated protein oxidation, as monitored by protein nitrotyrosine content, was significantly diminished. This was accompanied by reduced neointimal proliferation, as monitored by intimal thickness and intimal/medial ratio, in Nox2-/- compared to wild-type mice. In addition, Nox2 deficiency led to reduced cellular proliferation and leukocyte accumulation. These data indicate that Nox2-mediated oxidant production has a requisite role in the response to tissue injury.
Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Zhiping
Z
Chen
John F
JF
Keaney
Eberhard
E
Schulz
Bruce
B
Levison
Lian
L
Shan
Masashi
M
Sakuma
Xiaobin
X
Zhang
Can
C
Shi
Stanley L
SL
Hazen
Daniel I
DI
Simon
D000818:Animals; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D045303:Cytochromes b / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D005263:Femoral Artery / Q000293:injuries / Q000473:pathology / Q000502:physiology*; D007150:Immunohistochemistry; D007962:Leukocytes / Q000502:physiology; D008562:Membrane Glycoproteins; D051379:Mice; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000502:physiology*; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
D008562:Membrane Glycoproteins; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D013481:Superoxides; D045303:Cytochromes b; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases