Alterations in cell adhesion proteins and cardiomyopathy

Table 1 Adhesive proteins-associated cardiomyopathies in human and murine models

Adhesive junctionalcomponent (Gene)	Cardiac phenotype
	Human cardiomyopathy	Ref.	Mouse model of cardiomyopathy	Ref.
N-cadherin (CDH2)	DCM, HCM, heart failure	[26-28]	GOF: DCM, cardiac calcification LOF: DCM, ventricular arrhythmia, sudden cardiac death HET: Normal cytoarchitecture, induced arrhythmia	[42,58]
				[43,44]
				[25]
β-catenin (CTNNB1)	HCM, heart failure	[27,61]	GOF: DCM, premature death	[53]
			LOF: Normal cardiac function, blunt response to induced hypertrophy	[50,51]
			HET: Normal cardiac structure, reduced response to hypertrophy	[52]
Plakoglobin (JUP)	AC, Naxos disease	[30,31]	GOF (wild-type): adipocyte accumulation, inflammation	[46]
		[27,32,34,35]	GOF (Naxos mutation): adipocyte accumulation, inflammation, cardiac dysfunction, apoptosis	[47,48]
			LOF (perinatal): early onset of cardiomyopathy, severe ventricular arrhythmia	[45]
			LOF (adult): dilated cardiomyopathy, apoptosis, inflammation, fibrosis	[62]
			HET: Aged animals with right ventricular dilation, arrhythmia	[49]
αT-catenin (CTNNA3)	DCM, AC	[9,36]	LOF: DCM, arrhythmia, area composita defects	[56]
αE-catenin (CTNNA1)	Post-MI ventricular rupture Heart failure	[29]	LOF: Progressive DCM, RV dilation, MI-induced ventricular rupture	[54]
			HET: MI-induced ventricular rupture	[29]
mXinα (mXinα, Cmya1)	None	None	LOF: HCM, arrhythmia, ID defects	[23]
Desmoglein2 (DSG2)	AC	[63]	LOF: Dying cardiomyocytes with calcification, complete dissociation of intercalated discs, fibrotic replacement	[64]
			GOF (N266S): Sudden death, ventricular arrhythmias, cardiac dysfunction, biventricular dilatation, aneurysms	[59]
			GOF (N271S): Intercellular space widening, fibrosis, increased arrhythmia, lower sodium channel current density	[65]
Desmocollin2 (DSC2)	AC	[66-68]	None
Plakophilin2 (PKP2)	AC	[63,69]	HET (haploinsufficiency): Impaired ventricular conduction, sodium channel dysfunction	[60]
Desmoplakin (DSP)	AC, Carvajal syndrome, heart failure	[38,41,56]	LOF: Impairs cardiac morphogenesis and leads to high embryonic lethality	[46,47,57]
			GOF (R283H): Apoptosis, fibrosis, lipid accumulation, ventricular enlargement and cardiac dysfunction	[58]
			HET: Excess adipocytes, fibrosis, increased apoptosis, cardiac dysfunction, and ventricular arrhythmias	[57]

DCM: Dilated cardiomyopathy; HCM: Hypertrophic cardiomyopathy; AC: Arrhythmogenic cardiomyopathy; LOF: Loss-of-function; GOF: Gain-of-function; HET: Heterozygous; ID: Intercalated disc.