. 2021 Mar 5;10(3):387. doi: 10.3390/antiox10030387

Table 1.

Studies on defective autophagy in endothelial cells: role in atherothrombosis.

In Vitro/In Vivo Model	Results	References
- shAtg7 HUVECs treated with 50 μg mL⁻¹ oxLDLs - Atg7^endo mice (fl/fl;VE-Cadherin Cre) mice - HFD-fed apoE^−/−Atg7^endo mice	↓ LC3-II/ LC3I, ↑ oxLDLs ↑ intracellular ¹²⁵I-LDL chol ↑ transcytosis intracellular ¹²⁵I-LDL chol ↑ dil-oxLDLs in RPE and choroidal endothelium ↑ atherosclerotic lesion size ↑ necrotic area	[136]
- HUVECs treated with 50 mg/mL oxLDLs - ApoE^−/− mice	↓ mTOR, ↑ Atg13, ↓p-Atg13 ↑ apoptosis of endothelial cells ↑ atherosclerotic lesion areas ↑ instability of plague, ↑ lipid deposition, ↑SMCs ↑ macrophage cell area ↑ MMP-2 MMP-9 activity ↑ ICAM-1, VCAM-1; IL-6, IL-8	[141]
- HFD-fed apoE^−/−Atg5^flox/flox mice - HFD-fed apoE^−/−Atg5^flox/flox; VE-cadherin-cre mice - Atg5^flox/flox;VE-cadherin-cre - Atg7^flox/flox;VE-cadherin-cre mice - wortmannin-inhibited autophagy in HUVECs exposed to high SS - sh-Atg5 lentivirus in HUVECs exposed to high SS - HFD-fed Atg5 or Atg7-deficient mice	↑ plague formation, ↑ plague size in atheroresistant regions ↑ serum glucose levels - disturbed endothelial alignment in response to flow ↓ KLF2, ↑ ICAM-1, and MCP-1 ↑; p53, ↑ p16, ↑ SA-β-gal	[143,150]
- HUVECs treated with 20–40 μg/mL oxLDLs - LDLR knockout mice	↑ Beclin-1, ↑LC3-II/ LC3I, ↑ LOX-1 ↑ mtDNA damage, ↑ TLR9, ↑ CD45 and CD68	[147]
- BAECs treated with 100 μM oxLDLs	↓ Beclin-1, LC3-II/LC3I, ↑ LOX-1 ↑ MDA, ↑apoptosis	[148]
- young HUVECs or HAECs transfected with adenovirus-mediated overexpression of ARG2 or inactive ARG2 (H160F) - HFD-fed apoE^−/−Arg2^+/+ mice - HFD-fed apoE^−/−Arg2^−/− mice	↓ LC3II/LC3I, Atg12–Atg5 conjugate, ↑ p62 ↑ SA-β-gal ↓ PRKAA-T172/PRKAA, ↑ RICTOR ↑ AKT-S473/AKT, RPS6-S235/236:RPS6 ↑ TP53-S15/TP53	[149]
- HUVECs treated with 100 μg/mL oxLDLs	↓ miRNA-126, ↓ cell viability ↑ caspase-3 activity, ↑ apoptosis rate, ↑ LDH release - defective autophagic flux and degradation ↑ Beclin-1, ↑ LC3-II/LC3I, ↑ p62, ↑ p-mTOR/mTOR ↑ p-PI3K p85/ PI3K p85, ↑ p-Akt/Akt	[152]
- young HUVECs transfected with miRNA216a - HAECs transfected with miRNA216a - HCAECs transfected with miRNA216a - young HUVECs transfected with iRNA216a and treated with 100 μg/mL oxLDLs	↓ Beclin-1 and Atg5 mRNA and protein levels ↓ LC3II/LC3I, ↑ oxLDL accumulation ↑ monocyte adhesion	[153]
- CD31⁺ aortic endothelial cells derived from HFD-fed apoE^−/− mice - young HUVECs transfected with miRNA214-3p and treated with 100 μg/mL oxLDLs	↓ Arg5 and Atg12, ↑ p62, ↓ LC3II ↑ oxLDL accumulation, ↑ monocyte adhesion ↓ cell viability	[154]
- HUVECs treated with 25, 50, or 100 μg/L oxLDLs - HUVECs transfected with si-LncRNAFA2H-2 and treated with 25, 50, or 100 μg/L oxLDLs - HFD-fed apoE^−/− mice infected with si-LncRNAFA2H-2	↑ VCAM-1, MCP-1, TNF-α ↑ IL-6, IL-1 β, IL-18, IL-8 ↓ IL-10 - impaired autophagic degradation ↑ LC3-II/LC3I, p62, LAMP1 ↓ cathepsin D ↓ LncRNAFA2H-2, ↑ MLKL ↓ p-PI3K, p-Akt, p-mTOR, ↑ AMPK ↑ lesion areas, proliferative and disarranged intima ↑ lipid-laden foam cells ↑ cholesterol crystals	[155]

↑ increase, ↓ decrease. Atg: autophagy-related protein; HUVECs: human umbilical vein endothelial cells; HFD: high fat diet; apoE^−/−: apolipoprotein E-deficient; LC3-II: microtubule-associated protein light chain 3-II; ¹²⁵I-LDL: intracellular low density lipoprotein; Chol: cholesterol; dil-oxLDL: fluorescently labelled oxLDLs; RPE: retinal pigment epithelium; mTOR: mammalian target of rapamycin SMCs: smooth muscle cells; MMP: metalloproteinase; ICAM-1: intracellular adhesion molecule 1; VCAM-1: vascular cell adhesion molecule 1; IL: interleukin; KLF-2: Krüppel-like Factor 2; MCP-1: monocyte chemoattractant protein-1; SA-β-gal: senescence associated β-galactosidase; SS: shear stress; Akt: protein kinase B; TLR9: toll like receptor-9; LDLR: low density lipoprotein receptor; LOX-1: Lectin-like oxidized low-density lipoprotein receptor-1 BAECs: Bovine aortic endothelial cells; HAECs: human aorta endothelial cells; ARG: arginase; PI3K: phosphatidylinositol 3-kinases; LDH: lactate dehydrogenase; HCAECs: human coronary artery endothelial cells; TNF-α: tumor necrosis factor- α; MLKL: mixed lineage kinase domain-like protein; AMPK: AMP-activated protein kinase.