Table 2.

Adamts knockout mice and overexpression in vivo. AB, aortic banding-induced cardiac hypertrophy; BAV, bicuspid aortic valve; AngII, angiotensin II; PAH, pulmonary arterial hypertension; PPS, pentosan polysulfate; TAAD, thoracic aortic aneurysms and dissections. Genetic manipulation is in mice if not otherwise specified.

enzyme	human disease modelled	intervention	genetic manipulation	effect	reference
ADAMTS-1	arterial injury	carotid artery ligation	transgenic Adamts1 overexpression on Apoe−/− background	enhanced intimal thickening	[107]
	TAAD	AngII	Adamts1+/−	increased incidence of aneurysm and mortality, hypotension, medial degeneration	[109]
	TAAD	AngII	lentivirus-mediated Adamts1 knockout	increased incidence of aneurysm and mortality, hypotension, medial degeneration	[109]
ADAMTS-2	cardiac hypertrophy	AB	Adamts2−/−	increased cardiac hypertrophy, fibrosis and dysfunction	[110]
	cardiac hypertrophy	AB	transgenic Adamts2 overexpression	decreased cardiac hypertrophy, fibrosis and dysfunction	[110]
ADAMTS-4	atherosclerosis	high fat diet	Adamts4−/−; ApoE−/−	increased plaque stability; decreased lipid deposition; decreased macrophage infiltration; decreased versican and aggrecan degradation	[111]
	TAAD	high fat diet/AngII	Adamts4−/−	reduced incidence of aneurysm and mortality, decreased aortic destruction and versican degradation, decreased macrophage infiltration, decreased VSMC apoptosis	[112]
ADAMTS-5	TAAD	AngII	Adamts5−/−	reduced blood pressure, increased aortic dilation, accumulation of versican	[50]
	—	—	Adamts5−/−	aortic and pulmonary valve anomalies, BAV, accumulation of aggrecan and versican	[51,53,113,114]
ADAMTS-6	—	—	Adamts6−/−	congenital heart defects such as double outlet right ventricle, ventricular hypertrophy, atrial and ventricular septal defects	[115]
ADAMTS-7	atherosclerosis	high fat diet	Adamts7−/− ApoE−/−	reduced atherosclerotic lesion area	[116]
	vascular injury	wire injury	Adamts7−/−	reduced neo-intima formation, increased re-endothelialisation	[116,117]
	vascular injury	balloon injury	siRNA-mediated Adamts7 knockdown in rats	reduced intimal thickening	[118]
	vascular injury	balloon injury	transgenic Adamts7 overexpression in rats	increased intimal thickening	[118]
ADAMTS-8	PAH	hypoxia-induced PAH	Adamts8ΔSM22α	decreased right ventricular systolic pressure and right ventricular hypertrophy	[119]
	PAH	hypoxia-induced PAH	Adamts8ΔαMHC	decreased cardiac hypertrophy, fibrosis and right ventricular dysfunction	[119]
ADAMTS-9			Adamts9+/−	thickened aortic valve leaflets, myxomatous mitral valves, abnormal myocardial projections and interventricular septae, increased adventitial thickness associated with versican accumulation in the aorta	[120]
ADAMTS-16	hypertension	—	Adamts16−/− rats	lower systolic blood pressure, decreased arterial stiffness and thickness of the tunica media	[121]
ADAMTS-19	—	—	Adamts19−/−	aortic regurgitation, aortic stenosis, BAV	[122]