Table 1.
Genetic studies implicating autophagy in atherosclerosis.
| Genotype | Specificity | Observations | References |
|---|---|---|---|
| Wip1−/− | Whole body | Upregulation of autophagy-dependent cholesterol efflux through the Atm-mTOR-dependent signaling pathway inhibits lipid deposition. | (5) |
| TFEBTG | Macrophage | Reverses autophagic dysfunction of plaques, enhances phagocytosis of p62-rich protein aggregates, inhibits macrophage apoptosis and pro-inflammatory IL-1b levels, thereby reducing atherosclerosis. | (6) |
| SYK−/− | Macrophage | Regulation of MHC-II through enhanced autophagy to reduce IgG levels and inhibit atherosclerosis. | (7) |
| SR-BI−/− | Macrophage | SR-BI deletion reduces autophagy levels by decreasing the base of TFEB, a major regulator of autophagy, and by inhibiting the recruitment of the VPS34-Beclin-1 complex. | (8) |
| LAMP-2A−/− | Macrophage | Blocking the degradation of NLRP3 protein via the chaperone-mediated autophagy pathway aggravates the inflammatory response and promotes atherosclerosis | (9) |
| Arg2−/− | Whole body | Knockdown of Arg2 reduces RPS6KB1 levels, enhances PRKAA signaling and aortic endothelial cell autophagy, and reduces atherosclerotic lesion formation. | (10) |
| Atg14TG | Macrophage | Overexpression of ATG14 promoted the fusion of autophagic vesicles with lysosomes, promoted lipid degradation, reduced oxidized Ox-LDL-induced apoptosis and inflammatory responses, and upregulated the number of Treg cells, thereby reducing atherosclerotic lesions. | (11) |
| Endothelial cell | Absence of endothelial autophagy significantly increases lipid accumulation within the vessel wall. | (12) | |
| Atg7−/− | T cell | Inhibition of T-cell autophagy reduced the number of CD4+, CD8+ and NKT cells, perhaps reducing atherosclerosis. | (13) |
| Vascular smooth muscle cells | Impaired autophagy in SMC promotes the accumulation of debris mitochondria, leading to more oxidative stress and resulting in an unstable plaque phenotype. | (14) | |
| Atg5−/− | Endothelial cell | Defective endothelial cell autophagy not only inhibits the alignment of endothelial cells with the direction of blood flow, but also promotes inflammatory, apoptotic and senescent phenotypes. | (15) |
| Macrophage | Inhibition of autophagy further activates NLRP3 to promote inflammation and accelerate atherosclerosis | (16) |