TABLE 2.

Cardiac output of the Hippo–YAP1/TAZ pathway in cell and animal models.

Gene	Model		Promoter	Output
YAP1	Mouse	CKO	Tnnt2-Cre	Cardiac hypoplasia (reduced ventricular chamber size, ventricular septal defects, peripheral edema, and pericardial effusion) (von Gise et al., 2012)
	Mouse	CKO	Nfatc1IRES–Cre/+	Less CM proliferation, impaired compact myocardium, and early postnatal lethality (Artap et al., 2018)
	Mouse	CKO	α-MHC-Cre	Blunted cardiac hypertrophy and amplified CM apoptosis and fibrosis; cardiac dilatation and dysfunction after TAC (Byun et al., 2019)
	Mouse	CKO	Nkx2.5-cre	Lack of healthy myocardial tissue in the left ventricle wall and an enhancing fibrotic infarct zone following MI (Xin et al., 2013a)
	Mouse	CKO	α-MHC-Cre	Thinned septal and posterior wall, and chamber dilation (Del Re et al., 2013).
	Mouse	CKO	α-MHC-Cre	Increasing CM apoptosis, fibrosis, enlarging infarct size, and impairing cardiac function (Del Re et al., 2013)
	Mouse	Overexpression	Adeno-associated virus subtype 9: human YAP1	Alleviating MI injury and ameliorating cardiac function (Lin et al., 2014)
	Mouse	YAP5SA (active YAP1) overexpression	αMyHC-Cre-ERT2	Re-entering the cell cycle and reprogramming into more primitive and fetal cell states; thickened ventricular walls and smaller chambers (Monroe et al., 2019)
	Mouse	YAPS112A (active YAP1) overexpression	α-MHC	Increased myocardial tissue and reduced LV fibrosis in neonatal heart (Xin et al., 2013a)
	AC16 human CMs	Overexpression	Lentiviral vectors	Reducing CM apoptosis, cell hypertrophy, and ROS generation after IR (Khan et al., 2019)
WWTR1 (TAZ)	Zebrafish	CKO	CRISPR/CAS9	CM proliferation arrest, reduced cardiac trabeculation, and immature trabecular bridges (Lai et al., 2018)
WW45	Mouse	CKO	Myh6-Cre	Sustained YAP1 activation in CMs with cell-cycle re-entry, increased de-differentiation, and decreased apoptosis; cardiac dysfunction, severe heart failure, and enhanced mortality in response to TAC (Ikeda et al., 2019a, b)
SAV1	Mouse	CKO	Nkx2.5-cre	Ventricular septal defect and abnormal heart growth (thickening of ventricular walls, expansion of trabecular and ventricular myocardial layers, and enlargement of ventricular chambers) (Heallen et al., 2011)
	Mouse	CKO	Myh6CreERT2 αMHC-mcm	Presenting renewal capacity: increase in cell number and myocardial regeneration following cardiac apex resection in postnatal hearts; increased LV CMs, less fibrosis, and improved cardiac function after MI in adult heart (Heallen et al., 2013; Leach et al., 2017)
RASSF1A	Mouse	cardiomyocyte-specific KO	α-MHC-Cre	Basal nondistinctive cardiac phenotype or functional abnormality; reduced apoptosis, fibrosis, and hypertrophy after TAC (Del Re et al., 2010)
	Mouse	KO	NS	Increased hypertrophic response, reduced cardiomyocytes apoptosis, and increased fibrosis after TAC (Del Re et al., 2010)
MST1/2	Mouse	CKO	Nkx2.5-cre	Ventricular septal defect and abnormal heart growth (Heallen et al., 2011)
MST1	Mouse	DN-MST1 overexpression	CMV-Cre	Reducing the size of MI in the area at risk, and decreasing CM apoptosis (Nakamura et al., 2016)
	Mouse	DN-MST1 overexpression	α-MHC	Reduced left ventricular remodeling, improved left ventricular function, and enhanced survival rate after MI (Maejima et al., 2013)
LATS2	Mouse	LATS2 overexpression	α-MHC	Reduced left ventricular systolic and diastolic dysfunction, and smaller left/right ventricle (Matsui et al., 2008)
	Mouse	DN-LATS2 overexpression	α-MHC	Reduced CM apoptosis and enhanced biventricular hypertrophy following TAC (Matsui et al., 2008)
	Mouse	CKO	Nkx2.5-cre	Ventricular septal defect and abnormal heart growth (Heallen et al., 2011)
LATS1/2	Mouse	LATS1/2 CKO; YAP1/TAZ CKO	WtCreERT2 allele	Successful survival past E15.5 without defects in coronary vasculature (Xiao et al., 2018)
	Mouse	CKO	WtCreERT2 allele	Failing to survive past E15.5; smaller hearts with less compacted myocardium (Xiao et al., 2018)
	Mouse	CKO	Myh6CreERT2	Presenting renewal capacity: increasing cell number and regenerating the myocardium following cardiac apex resection in postnatal hearts; increased LV CMs, less fibrosis, and improved cardiac function after MI in adult heart (Heallen et al., 2013)
	Zebrafish	DKO	Myh6; Myl7	Enhanced Hand2 expression and CM differentiation (Schindler et al., 2014; Fukui et al., 2018)

NS, not specified, where the specific promotors have not been validated; YAP1, Yes-associated protein 1; TAZ, PDZ-binding motif; CKO, cardiac knockout; KO, knockout; DN, dominant negative, MI, myocardial infarction; CM, cardiomyocytes; TAC, transverse aortic constriction; IR, ischemia–reperfusion; ROS, reactive oxygen species.