Involvement of the Nicotinamide Adenosine Dinucleotide Phosphate Oxidase Isoform Nox2 in Cardiac Contractile Dysfunction Occurring in Response to Pressure Overload
David J. Grieve, PhD,
Jonathan A. Byrne, PhD, MRCP,
Anjana Siva, PhD, MRCP,
Joanne Layland, PhD,
Sofian Johar, MRCP,
Alison C. Cave, PhD and
Ajay M. Shah, MD, FAHA*
King’s College London, Cardiovascular Division, Guy’s, King’s, and St. Thomas’ School of Medicine, London, England
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Figure 1 Effect of pressure overload on cardiac fibrosis. (A) Interstitial collagen assessed in left ventricular (LV) sections stained with Picrosirius red. (B to D) messenger ribonuclerc acid expression of procollagen I, procollagen III, and fibronectin. Data are mean ± SEM from six animals. *p < 0.05 versus corresponding sham;  p < 0.05 versus banded Nox2–/–. WT = wild type.
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Figure 2 Left ventricular (LV) function in isolated ejecting hearts from wild-type (WT) and Nox2–/– mice across a range of LV end-diastolic volumes (EDV). Changes in A and D: maximum rate of rise of LV pressure (LVdP/dtmax); changes in B and E: maximum rate of fall of LV pressure (LVdP/dtmin); changes in C and F: stroke work (SW). Data are mean ± SEM from eight animals. *p < 0.05 banded (solid squares) versus sham (open squares).
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Figure 3 Representative examples of left ventricular (LV) pressure-volume analyses in banded (solid squares) and sham-operated (open squares) wild-type (WT) and Nox2–/– mice. (A and D) Steady-state pressure-volume loops. (B and E) End-systolic pressure relation (ESPVR). (C and F) End-diastolic pressure volume relation (EDPVR).
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Figure 4 Effect of pressure overload on cell shortening (CS) in cardiomyocytes from wild-type (WT) and Nox2–/– mice. (A and B) Representative traces of myocyte contraction. (C and D) Mean ± SEM from  60 cells from four hearts. Dark columns = banded mice; lighter columns = shams. *p < 0.05 versus sham.
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Figure 5 Effect of N-acetylcysteine on cardiac function assessed (A to C) by echocardiography and (D to F) in isolated ejecting hearts. Light columns = control animals; darker columns = N-acetylcysteine-treated animals. Data are mean ± SEM from eight animals. *p < 0.05 versus corresponding control.
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Figure 6 Representative left ventricular (LV) sections from wild-type (WT) mice stained for 3-nitrotyrosine (20x magnification). (A) Sham, (B) banded; (C) N-acetylcysteine-treated sham; (D) N-acetylcysteine-treated banded.
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Figure 7 Left ventricular (LV) function in isolated ejecting hearts from wild-type (WT) and Nox2–/– mice eight weeks after surgery. Changes in (A and D): LVdP/dtmax; (B and E) LVdP/dtmin; and (C and F) cardiac work (CW). Data are mean ± SEM from five to six animals. *p < 0.05 banded (solid squares) versus sham (open squares).
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