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Role of p47phox and Nox2 in the Promotion and Impairment of Collateral Growth
Author(s) -
Distasi Matthew,
Ingram David,
Miller Steven,
Unthank Joseph
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.682.18
Subject(s) - nadph oxidase , medicine , endocrinology , nox4 , reactive oxygen species , oxidative stress , chemistry , femoral artery , biochemistry
Anti‐oxidant therapy implicates a role for reactive oxygen species (ROS) in both successful collateral growth (CG) and its impairment in models of chronically elevated oxidative stress, including obese mice. NAD(P)H oxidase (Nox) is a major source of vascular ROS. This study investigates the roles of the Nox subunits p47 phox and Nox2 in CG (assessed as % increase in collateral diameter compared to same animal control artery) in lean and obese mice. C57BL/6, p47 phox−/− , and Nox2 −/− mice were fed either standard chow (Lean) or a high‐fat (60% kcal from lard) diet to induce obesity. In lean mice after femoral artery ligation, significant CG occurred in wild‐type (WT) and Nox2 −/− mice (171±43 and 112±21%, respectively, p<0.05) but not in p47 phox−/− mice (52±31%). In obese mice, CG was greatly suppressed in WT mice (25±13%); however, whole body ablation of both Nox2 and p47 phox attenuated the impairment (144±68 and 107±7% increase in collateral diameter, respectively, P<0.05). RT‐PCR analysis demonstrated an increase in p47 phox (1.9X, P<0.02) and Nox2 (1.6X, P<0.07) subunit expression in obese vs. lean arteries. Transplantation of WT bone marrow into lean p47 phox−/− did not prevent the suppression of CG. In conclusion, these data suggest that tissue resident p47 phox is required for CG in lean mice and that obesity‐induced increases in p47 phox and Nox2 expression mediate the impairment of CG in obese mice. Grant Funding Source : NIH T32 HL007910 ‐26