TABLE 1.

Selected animal model studies suggesting promising therapeutic strategies to combat cardiac fibrosis.

Approaches	Methods	Model	References
Ablating activated cardiac fibroblasts	CAR-T	Ang II/phenylephrine treatment in mice	Aghajanian et al. (2019)
Suppressing activation of cardiac fibroblasts	Macrophage specific deletion of microRNA-21	pressure overload in mice	Ramanujam et al. (2021)
Targeting TGFβ1	TGFβ1-neutralizing antibody (1D11)	pressure overload in mice	Kassiri et al. (2009)
MMP inhibition	PD166793	pressure overload in mice	Kassiri et al. (2005), Kandalam et al. (2011)
	Reduction of MT1-MMP expression	pressure overload in mice	Zile et al. (2014)
TIMPs	Deletion of TIMP1	pressure overload, Ang II treatment in mice	Takawale et al. (2017b)
	TIMP2-contained exosomes	Myocardial infarction in mice	Ni et al. (2019)
	Intracoronary infusion of rTIMP3	ischemia-reperfusion in pigs	Barlow et al. (2017)
	Myocardial injection of MMP-responsive hydrogel releasing rTIMP3	Myocardial infarction in pigs	Purcell et al. (2018)
	Cardiac-restricted overexpression of TIMP4	Pressure overload in mice	Yarbrough et al. (2014)
Exercise	Moderate-intensity exercise training	Aging in mice	Pei et al. (2021)
	Exercise hypertrophic preconditioning	Pressure overload in mice	Lin et al. (2021)

Ang II, angiotensin II; CAR-T, chimeric antigen receptor T-cells; MMP, matrix metalloproteinase; MT1-MMP, membrane type 1-MMP; rTIMP3, recombinant tissue inhibitor of metalloproteinase-3; TGFβ1, transforming growth factor β1.