Table 1.
Selected studies of NADPH oxidase in models of vascular disease and stroke
| Mouse model | Disease model | Effects | Refs |
|---|---|---|---|
| Hypertension | |||
| Global knockout, Nox1−/− | Ang II | Decreased BP and O2•− levels, no change in medial hypertrophy and increased NO bioavailability | 72 |
| Ang II | Decreased BP and O2•− levels and medial hypertrophy | 71 | |
| Transgenic, NOX1 overexpression in VSMCs | Ang II | Increased BP and O2•− levels and medial hypertrophy | 69 |
| Double transgenic, Nox1−/−/TTRhRen | TTRhRen | No change in BP, decreased O2•− levels and renal fibrosis | 203 |
| Global knockout, Nox2−/− | Ang II | No change in BP, decreased O2•− levels and 3-nitrotyrosine expression | 204 |
| 2K1C | Decreased BP (minimal) and increased NO bioavailability | 56 | |
| Ang II | Increased NO bioavailability in afferent renal arterioles, and decreased constrictor responses to Ang II and adenosine | 205 | |
| Double transgenic, Nox2−/−/TTRhRen | TTRhRen | No change in BP, decreased O2•− levels | 206 |
| Transgenic, NOX2 overexpression in endothelium | Ang II | Increased BP, increased O2•− levels in the endothelium only | 207 |
| Global knockout, p47phox−/− | Ang II | Decreased BP and O2•− levels | 208 |
| DOCA–salt | Decreased BP and O2•− levels | 112 | |
| BMP4 | Decreased BP, increased NO bioavailability | 209 | |
| Adoptive transfer of T lymphocytes from wild-type and p47phox−/− mice to Rag−/− mice | Ang II | p47phox−/− T lymphocytes: decreased BP and O2•− levels, increased NO bioavailability (versus wild-type T lymphocytes) | 115 |
| Atherosclerosis | |||
| Double knockout, Nox2−/−/ApoE−/− | ApoE−/−, HFD | Decreased lesion area in the descending aorta, decreased intimal thickening, decreased O2•− levels and increased NO bioavailability | 81 |
| ApoE−/−, HFD | No change in lesion area in the aortic sinus | 210 | |
| Double knockout, p47phox−/−/ApoE−/− | ApoE−/−, HFD | No change in lesion area in the aortic sinus | 211 |
| ApoE−/−, chow and HFD | No change in lesion area in the aortic sinus, decreased lesion area in the descending aorta | 212 | |
| ApoE−/−, HFD | Decreased lesion area in the descending aorta (p47phox−/− in either vessel-derived or bone marrow-derived cells), decreased oxLDL levels (p47phox−/− in bone marrow-derived cells) and decreased adhesion molecule expression (p47phox−/− in vessel wall) | 213 | |
| Restenosis after arterial injury | |||
| Global knockout, Nox1−/− | Wire-induced injury | Decreased neointimal formation | 76 |
| Transgenic, NOX1 overexpression in VSMCs | Wire-induced injury | No effect on neointimal formation | 76 |
| Adenoviral-mediated overexpression of NOXA1 in VSMCs | Wire-induced injury | Increased neointimal formation, increased O2•− levels | 63 |
| Global knockout, Nox2−/− | Wire-induced injury | Decreased neointimal formation, decreased leukocyte accumulation in the neointima | 214 |
| Cerebral ischaemia | |||
| Global knockout, Nox2−/− | MCAO | Decreased infarct volume, ICAM1 expression and neutrophil infiltration | 54 |
| MCAO | Decreased infarct volume | 55 | |
| MCAO | Decreased infarct volume | 128 | |
| MCAO | Decreased infarct volume (Nox2−/− mice), no change in infarct volume after bone marrow transplant (wild-type bone marrow to Nox2−/− mice, Nox2−/− bone marrow to wild-type mice) | 129 | |
| MCAO | Decreased infarct volume in males only, decreased O2•− production by circulating T cells | 116 | |
| MCAO | Protective effect of apocynin (decreased infarct volume) absent in Nox2−/− mice | 53 | |
| Global knockout, Nox1−/− | MCAO | Increased cortical infarct volume | 131 |
| MCAO | Decreased infarct volume | 132 | |
| Global knockout, Nox4−/− | MCAO | Decreased infarct volume | 130 |
2K1C, two kidneys one-clip; Ang II, angiotensin II; APOE, apolipoprotein E; BMP4,bone morphogenetic protein 4; BP, blood pressure; DOCA, deoxycorticosterone acetate; HFD, high-fat diet; ICAM1, intercellular adhesion molecule 1; MCAO, middle cerebral artery occlusion; NO, nitric oxide; NOX1, NADPH oxidase 1; NOXA1, NOX activator 1; O2•−, superoxide; oxLDL, oxidized low-density lipoprotein; RAG, V(D)J recombination-activating protein; TTRhRen, transgenic mice expressing human renin; VSMC, vascular smooth muscle cell. Table modified from REF. 228.