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Differential response of cardiac NOX‐2 and ‐4 to mild and severe pressure overload
Author(s) -
Bradley Jessica M,
El Hajj Milad C,
Mouton Alan J,
El Hajj Elia C,
Gardner Jason D
Publication year - 2013
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.27.1_supplement.1128.13
Subject(s) - nox , pressure overload , oxidative stress , myocardial infarction , medicine , cardiology , ventricular remodeling , cardioprotection , nadph oxidase , heart failure , hemodynamics , endocrinology , chemistry , cardiac hypertrophy , organic chemistry , combustion
Heart failure results when compensatory mechanisms fail to overcome injury and hemodynamic overload often caused by pressure overload (PO), myocardial infarction, diabetes, or hypertension. Oxidative stress, via NADPH oxidases, has been shown to exacerbate PO‐induced left ventricular (LV) remodeling. However, individual NOX isoforms may have different roles in LV remodeling. Our goal was to examine the role of NOX‐2 and ‐4 during PO‐induced cardiac injury. We hypothesized that severe PO causes an imbalance of NOX‐2/NOX‐4, favoring the formation of oxidative stress and resulting in a loss cardioprotection. PO was surgically induced in male C57/BL6 mice via transverse aortic constriction (TAC: mild‐26g or severe‐27g needle). After 4 wks, analysis of LV homogenates indicated that mild TAC resulted in increased protein expression of NOX‐2 and ‐4 compared to Sham. Mild TAC also led to marked increases in lysyl oxidase (LOX), TGF‐β, HIF‐1α, and collagens I and III. Yet, severe TAC resulted in attenuation of NOX‐4, as well as TGF‐β. LOX expression was further increased by severe TAC compared to mild. These results suggest that NOX‐2 and ‐4 are differentially regulated during the progression of cardiac remodeling, with NOX‐2 promoting adverse remodeling and NOX‐4 promoting compensatory remodeling.