Table 4 In vitro models of inherited cardiomyopathies
Disease | Modeling strategy: hiPSCs-CM genotype | Features | In vitro models | Ref. |
|---|---|---|---|---|
Hypertrophic cardiomyopathy (HCM) | CRISPR-edited MYH7 mutation | Increased contractile force Prolonged relaxation kinetics | EHT | |
CRISPR-edited MYBPC3 mutation | Increased contractile force Reduced beating frequency and relaxation time Higher spontaneous arrhythmic behavior | EHT | ||
Patient-derived BRAF mutation | Increased tissue size and twitch force Atrial natriuretic peptide gene expression | EHT | ||
Patient-derived PRKAG2 mutation | Glycogen accumulation Increased twitch force Increased AMPK activity | EHT | ||
CRISPR-edited ACTN2 mutation | Myofibrillar disarray Increased contractility Impaired relaxation Higher myofilament Ca2+ sensitivity Prolonged APD | EHT | ||
Dilated cardiomyopathy (DCM) | Patient-derived TNNT2 mutation | Shortened sarcomere length and sarcomere disarray Abnormal sarcomeric structure Defective calcium handling Impaired contractility | EHT | |
CRISPR-edited TNNT2 mutation | Reduced contractile force Shortened sarcomere length | EHT | ||
Patient-derived TTN mutation | Sarcomere disorganization Reduced contractile force Impaired mechano-/β-adrenergic stress responses | EHT | ||
CRISPR-edited TPM1 and VCL mutation | Sarcomere disorganization Reduced contractile force | 2D monolayer | ||
Patient-derived PLN mutation | Reduced contractile force Elevated ER stress with UPR activation | EHT | ||
Patient-derived RBM20 mutation | Titin splicing abnormality Sarcomere disarray Defective calcium handling | EHT | ||
Duchenne muscular dystrophy (DMD) | Patient-derived DMD mutation | ABD-1 mutation correction restored contractility and Ca²⁺ handling | 2D monolayer | |
Increased sensitivity to mechanical stress Defective calcium handling | ||||
Impaired contractility (rescued by myoediting) | EHT | |||
Lack of initial proliferative capacity Sarcoglycan mislocalization Elevated ER stress with adipogenesis and fibrosis | CO | |||
Arrhythmogenic cardiomyopathy (ACM) | Patient-derived PKP2 mutation | Defective calcium handling Excessive lipogenesis Increased apoptosis | CO | |
Reduced Cx43 High-rate pacing capture failure | EHT | |||
Patient-derived DSP mutation | Reduced desmoplakin Diastolic lengthening Defective calcium handling Impaired contractility | EHT | ||
Restrictive cardiomyopathy (RCM) | Patient-derived FLNC mutation | Increased passive tension Impaired relaxation velocity (rescued by trequinsin) | EHT | |
Mitochondrial cardiomyopathy (Barth Syndrome) | Patient-derived TAZ mutation | Sarcomere disorganization Reduced contractile force Increased oxidative stress | 2D aligned tissue |
