Table 2.

Source of ROS and transgenic or knockout mice model related to cardiovascular disease

Source of ROS	Product	Tg or KO mouse model	phenotype or related cardiovascular disease	Reference
Mitochondrial respiratory chain	O2•−	Mn-SOD -null	Cardiomyopathy (lethal in neonatal)	[49]
		heart/muscle specific Mn-SOD -null	Cardiomyopathy, heart failure	[50]
		peroxiredoxin3 Tg	Reduced LV remodeling and HF after MI	[51]
NADPH oxidase	O2•−	Nox2-null	Attenuated cardiac remodeling and PC effect	[54–56]
		gp91phox-null	Attenuated AII induced hypertrophy but not TAC	[58–60]
		p47phox-null / ApoE-null	Reduced atherosclerosis and AII induced AAA	[61, 62, 64]
		Nox2-/y / ApoE-null	Reduce atherosclerosis	[63]
		gp91 phox-null / ApoE-null	No significant effects on atherogenesis	[286]
		cardiomyoccyte-specific Rac1-null	Attenuated AII-induced hypertrophy	[57]
Xanthine oxidase	O2•−/H2O2	Xanthine oxidase-null	Inhibitors attenuated IR injury *	[73, 74]
Lipoxygenase	LOO•, LO•	5-LO+/− / LDL-R-null	Reduced atherosclerosis	[90]
		12/15-LO-null / LDL-R-null	Reduced atherosclerosis	[89]
		Leukocyte-12-LO-null / Apo E-null	Reduced atherosclerosis	[87, 88]
eNOS	O2•−, NO•, O	eNOS-null	Increased mortality after MI	[118]
			Promoted LV remodeling after TAC	[119]
			Prevented LV remodeling after TAC	[287]
			Attenuated or worsened IR injury	[288–291]
		eNOS-null / ApoE-null	Promoted atherosclerosis	[113]
		eNOS Tg	Reduced IR injury infarct size after MI	[120, 121]
		endothelium-specific eNOS Tg / ApoE-null	Promoted atherosclerosis	[114]
		endothelium-specific GCH Tg / ApoE-null	Reduced atherosclerosis	[116]
		endothelium-specific eNOS/GCH Tg / ApoE-null	Reduced atherosclerosis	[117]
		cardiomyocyte-specific eNOS Tg	Attenuated compensatory hypertrophy after MI	[122]
		eNOS-null / cardiomyocyte-specific eNOS Tg	Prevented LV remodeling after TAC	[123]
iNOS	NO•, OONO−	iNOS-null	Decreased mortality after MI	[128]
			Prevented LV remodeling after TAC	[129]
		iNOS-null / ApoE-null	Reduce datherosclerosis	[125–127]
		cardiomyocyte-specific iNOS Tg	Increased HF, AV block and sudden death	[130]
			No significant difference compared to wild type	[292]
			Prevented I/R injury and reduced infarct size	[293]
		cardiomyocyte-specific iNOS Tg / myo-null	Developed HF	[294]
nNOS	NO•, OONO	nNOS-null	Promoted LV remodeling after MI	[134, 135]
		nNOS-null / ApoE-null	Promoted atherosclerosis	[132]
		nNOS-null / eNOS-null	Increased mortality and hypertrophy	[137]
		cardiomyocyte-specific nNOS Tg	Prevented LV remodeling after TAC	[136]
MPO	HOCl, •OH	MPO-null	Promoted LV remodeling after MI	[295, 296]
	Tyr•, Cl2, NO2•	MPO-null / LDL-R-null **	Promoted atherosclerosis	[151]
		human-MPO-Tg / LDL-R-null **	Promoted atherosclerosis	[152]

Abbrebiations: AAA = abdominal aortic aneurysm; AII = angiotensin II; AV = atrio-ventricular; GH = GTP cyclohydrolase; HF=heart failure; IR = ischemia/reperfusion; LV = left ventricular; PC = preconditioning; TAC = transaortic constriction;

^*XO-null mice did not show significant change in heart, but several animal studies with xanthine oxidase inhibitors (e.g. allopurionol) attenuated I/R injury

^**bone marrow transplantation model