Table 1.
Genetic approaches for modulation of autophagy and mitophagy along with their impact on the cardiovascular system.
| Genetic Approach | Affected Process | Effects on Cardiovascular System | Reference |
|---|---|---|---|
| Mutation: dnPI3K | Autophagy stimulation | Cardiac aging attenuation; Longer lifespan; Improved cardiac functional reserve; Attenuated fibrotic and hypertrophic remodeling; Rejuvenated phenotype of cardiomyocytes; Lower lipofuscin accumulation. |
[37] |
| Mutation: Akt2 deletion | Autophagy stimulation | Improved contractile function and cardiomyocyte calcium homeostasis in aged mice. | [36] |
| Parkin and PINK1 silencing | Mitophagy inhibition | Increased apoptosis in VSMCs through oxLDL | [38] |
| Sirt3 overexpression | Mitophagy stimulation | Activation of deacetylation of Foxo3A and expression of Parkin; Inhibition of mitochondrial damage and apoptosis in cardiomyocytes; Diabetic cardiomyopathy development in a mouse model of diabetic cardiomyopathy |
[39] |
| Mst1 knockout | Mitophagy stimulation | Parkin upregulation; Increased mitochondrial translocation; Protection of diabetic mice myocardium |
[40] |
| BAG3 knockdown | Mitophagy inhibition | Alteration in the clearance of defective mitochondria; Increase in levels of toxicity within the cells and subsequent cell death; Heart failure. |
[41] |
| CsA and PINK1 knockout | Mitophagy inhibition | Downregulation of PINK1 and Parkin in senescent cardiomyocytes; Prevention of cardiomyocyte senescence |
[42] |
| Akt2 Knockout | Mitophagy stimulation | Upregulation of Foxo1-related BNIP3, PINK1, and Parkin; Maintaining of mitochondrial integrity; Cardiac aging prevention |
[36] |
| DUSP overexpression | Mitophagy inhibition | Inactivation of JNK pathway; better survival of myocardial tissue after ischemia/reperfusion |
[43] |
| SWI/SNF deletion | Mitophagy stimulation | Formation of small and fragmented mitochondria | [44] |
| FUNDC1 knockout | Mitophagy inhibition | Aggravation of cardiac injury in the I/R model | [44] |