Table 5 Targeting NADPH oxidases in skeletal muscle

[94]

♂ ApoE^-/- (16wks); ND or HFD (15.8% fat, 1.25% cholesterol) for 8wks; For 4wks; HFD + Nox2 inhibitor peptide (Nox2ds-tat) or HFD plus control sequence (scrambled, Scr)

↑ cholesterol and TGs in Scr and Nox2ds-tat; ↑ O₂ ^.- production in carotid arteries and atherosclerotic lesions throughout the aorta of HFD and Scr but ↓ in Nox2ds-tat; ↓ mRNA expression of p47phox and p22phox in Nox2ds-tat vs Scr; ↑ gene expression of VEGF, HIF1α, visfatin and MMP9 in carotid arteries of Scr, ↓ in Nox2ds-tat; ↑ MMP9 activity and protein levels in carotid arteries of Scr vs ND and ↓ in Nox2ds-tat

[90]

♂, gp91^-/-, ApoE^-/- and ApoE^-/-/p47^-/- (18wks); ND and HFD for 10wks (15% w/w fat, 34% kcal from fat)

↓ p47^-/- in gp91^-/- response of SMC in growth factors in vs WT; ↓ O₂ ^.- expression in aortas of p47^-/- vs WT; ↔ ApoE^-/- and ApoE^-/-/p47^-/- in serum lipid levels; ↓ lesion area throughout the aorta, ↔ in the aortic sinus in ApoE^-/-/p47^-/- vs ApoE^-/- HFD

[228]

♂ ApoE^-/-, ApoE^-/-/p47^-/- (16wks); ND

↔ basal O₂ ^.- levels in aorta that ↓ in ApoE^-/-/p47^-/- after inhibition of SOD; ↔ aortic lesion area, serum blood levels and aortic blood pressure

[233]

♂ and ♀ WT, gp91^-/- (30wks), ApoE^-/-, ApoE^-/-/gp91^-/- (24wks); HFD for 20wks in WT and gp91^-/- (15% w/w, 37.1% kcal from fat, 1.25% cholesterol, and 0.5% sodium cholate); ApoE^-/-and ApoE^-/-/gp91^-/- in ND

↓ O₂ ^.- production from peritoneal macrophages in gp91^-/- and WT; ↔ gp91^-/- and WT in plasma lipid profile and lesion area (♀: ↓ plasma TGs and ↑ lesions);

↓ plasma cholesterol & TGs (only in ♂ ApoE^-/-/gp91^-/- vs ApoE^-/-); ↓ 2-fold HDL and ↑ 60% of LDL in ApoE^-/-/gp91^-/- vs ApoE^-/-; ↔ aortic sinus lesion area in ApoE^-/-/gp91^-/- vs ApoE^-/-

[57]

♂ApoE^-/- & (12 and 19wks); WD (21% w/w fat, 40% kcal and 0.15% cholesterol) for 7 and 14wks

↓ superoxide production, ↑ NO bioavailability and ↓ lesion coverage in Nox2^-/yApoE^-/-

[229]

♂ and ♀ ApoE^-/-, ApoE^-/-/p47^-/- ; Bone marrow transplanted mice for 4wks in ND and then in WD (42% kcal from fat, 0.2% cholesterol) for 12wks; (Control: Bone marrow transplantation from ApoE^-/- to ApoE^-/-)

↓ VWO & BMO in atherosclerotic coverage, lesion size with fewer macrophages and O₂ ^.-production vs Control; ↔ BMO & VWO in total cholesterol, TGs, expression of p22phox and catalytic subunits of Nox1 and Nox4; ↓ BMO in oxLDL levels vs VWO and Control; ↓ VWO in gene expression and immunostaining of VCAM1, iCAM1 and P Selectin vs BMO and control

↓ ApoE^-/-/p47phox^-/- in neointimal hyperplasia after femoral injury vs ApoE^-/-; ↑ VSMC proliferation in ApoE^-/- vs ApoE^-/-/p47phox^-/-

[225]

ApoE^-/-, Nox2Tg ApoE^-/-(9-24wks); Sex, NS; ND

↑ O₂ ^.- in Nox2Tg ApoE^-/-; ↑ VCAM1 and macrophage recruitment in Nox2Tg ApoE^-/- only at 9wks; ↔ total plasma cholesterol, LDL, HDL, TGs, OxLDL lesion area, lesion progression and composition, macrophage recruitment and lipid deposition in Nox2Tg ApoE^-/-; Treatment with AngII for 4wks ↑ lesions in a dose-dependent manner similarly

[231]

♂ ApoE^-/- and Nox1^-/yApoE^-/- (12, 19 and 26wks); WD (21% w/w fat and 0.15% cholesterol) for 7,14, or 21wks

↑ VLDL/LDL, TGs, O₂ ^.- and intimal thickening in aortic sinus in Nox1^-/yApoE^-/-; ↔ plaque area in Nox1^-/yApoE^-/- ; ↓ collagen, SMCs and ↑ MMP-9 in aortic sinus lesions in Nox1^-/yApoE^-/-

[230]

♂ ApoE^-/- and Nox1^-/yApoE^-/- (24wks); HFD for 18wks (42% kcal from fat)

↓ aortic lesions, O₂ ^.- production and number of macrophages in lesions in Nox1^-/yApoE^-/-

[91]

♂ WT (28 wks old); HFD for 8wks (60% kcal from fat) or ND, a HFD subgroup treated with apocynin

↑ plasma insulin, glucose and HOMA-IR in HFD; ↓ glucose uptake from muscle and ↑ H₂O₂ in myofibres after insulin stimulation of HFD; GSH/GSSG ratio in muscle of HFD; ↑ Nox2 and p47phox protein expression in HFD muscle; ↓ insulin resistance in whole body and muscle and p47phox and Nox2 levels in muscle of HFD after treatment with apocynin

[239]

♂ WT and Nox2^-/y (18 and 42wks); ND or HFD (45% kcal from fat) for 3 or 9 months

↑↑ WT HFD and ↑ Nox2^-/y in BW, HOMA-IR and GTT; ↔ oxidative and glycolytic myofibres; ↑ Nox2, p22phox, p67phox and O₂ ^.-production in the muscle of WT HFD; ↑ Nox2^-/y HFD and ↓ WT HFD in Glut4 and Akt phosphorylation of muscle; ↑ Nox2, p22phox, p67phox and ↓ phosphorylated Akt and glucose uptake in myoblasts treated with palmitate or high concentration of glucose; ↓ phosphorylated Akt and glucose uptake in shRNA Nox2-expressing myoblasts after treatment with H₂O₂