Table 1.
Role of DNA and histone modification enzymes in experimental atherosclerosis and associated vascular diseases in vivo
| Animal models | Target | Phenotype | Reference |
|---|---|---|---|
| DNMT1Tg; ApoE−/− | DNMT1 | ↑ Plaques sizes ↑Macrophage inflammation ↑Increase PPAR-γ methylation ↓PPAR-γ |
(J. Yu, et al., 2016) |
| TET2KD; TET2OE | TET2 | OE↓Neointima hyperplasia KD↑ Neointima hyperplasia |
(R. Liu, et al., 2013) |
| Tet2OE; ApoE−/− Tet2KD; ApoE−/− | TET2 | OE↓ Plaque sizes, inflammation, ↑autophagy KD↑ Plaque sizes, inflammation, ↓autophagy |
(Peng, et al., 2016) |
| TET2ΔMye; LDLr−/− 10% TET2KO BMT | TET2 | ↑ Plaque sizes, IL-β-dependent inflammasome | (Fuster, et al., 2017) |
| TET2ΔHem BMT | TET2 | ↑ Plaque sizes, inflammatory cytokines/chemokines | (Jaiswal, et al., 2017) |
| EZH2OE; ApoE−/− | EZH2 | ↑ Plaque sizes, foam cell formation ↓ ABCA1-dependent cholesterol efflux |
(Lv, et al., 2016) |
| HDAC3KD; ApoE−/− | HDAC3 | ↑ Plaque sizes and vessel rupture in isografted vessels ↓EC survival |
(Zampetaki, et al., 2010) |
| HDAC3−/−; ApoE−/− | HDAC3 | ↓Plaques sizes ↑ Plaque stability |
(Hoeksema, et al., 2014) |
| HDAC9−/−; LDLr−/− | HDAC9 | ↑ Atherosclerotic plaques ↓Cholesterol efflux |
(Cao, Rong, et al., 2014) |
| HDAC9−/−; ApoE−/− | HDAC9 | ↑Plaque sizes and severity | (Azghandi, et al., 2015) |
| SIRT1TgEC; ApoE−/− | SIRT1 | ↓ Plaques sizes ↑Improved EC-dependent vasorelaxation ↑eNOS |
(Q. J. Zhang, et al., 2008) |
| SIRT1+/−; ApoE−/− | SIRT1 | ↑ Plaques sizes ↑NF-kB/LOX-1 pathway ↑Foam cell formation ↑Macrophage/T cell infiltration |
(Stein, Lohmann, et al., 2010) |
| SIRT1+/−; ApoE−/− | SIRT1 | ↑Endothelial activation, ↑ Vascular inflammation, - endothelium-dependent vasorelaxation p-eNOS (S1177), eNOS |
(Stein, Schafer, et al., 2010) |
| SIRT 1Tg; LDLr−/− | SIRT1 | Increased atherosclerotic lesions; Worse lipid profile; Increased Creb deacetylation |
(Qiang, et al., 2011) |
| SIRT1 ΔVSMC; ApoE−/− | SIRT1 | ↑ Atherosclerotic lesions; ↓ Fibrous cap thickness; ↑ VSMC DNA damage and senescence, media degeneration |
(Gorenne, et al., 2013) |
| SIRT1 ΔVSMC; ApoE−/−+Ang-II SIRT1 TgVSMC; ApoE−/−+Ang-II | SIRT1 | KO↑AAA formation and rupture, inflammaging KO↓ CR induced protection against AAA TG↓ AAA formation and rupture, inflammaging |
(H. Z. Chen, et al., 2016; Y. Liu, et al., 2016) |
| SIRT1 ΔVSMC+Ang-II | SIRT1 | ↑Disorganized elastic lamellae ↑Elastin fragmentation ↑ROS production, MMP2/9 activity ↑Aortic stiffness |
(Fry, et al., 2015) |
| SIRT1 T gVSMC+HFHS | ↓Arterial stiffness, inflammation, ROS | (Fry, et al., 2016) | |
| SIRT1ΔEC; ApoE−/− | SIRT1 | ↑ Atherosclerotic lesions | (Wen, et al., 2013) |
| SIRT1ΔMye | SIRT1 | ↑ Insulin resistance ↑Metabolic derangement ↑Hyperacetylation and activation of NF-kB |
(Schug, et al., 2010) |
| SIRT1ΔMye+Ang-II | SIRT1 | ↑ Incidence and severity of AAA ↑ M1 macrophages ↓M2 macrophages |
(Z. Zhang, et al., 2018) |
| SIRT2KD, SrRT2OE LDLr−/− | SIRT2 | OE↓Atherosclerotic lesion KD↑ Atherosclerotic lesion |
(B. Zhang, et al., 2018) |
| SIRT3−/−; LDLr−/− | SIRT3 | -Plaque size -Plaque vulnerability ↑ Weight gain |
(Winnik, et al., 2014) |
| SIRT6+/−; ApoE−/− | SIRT6 | ↑ Atherosclerotic lesion ↑ Necrotic core and unstable plaques |
(Z. Q. Zhang, et al., 2016) |
| SIRT6+/−; ApoE−/− | SIRT6 | ↑ Atherosclerotic lesion ↓ EC-dependent vasorelaxation |
(S. Xu, Yin, et al., 2016) |
| SIRT 6KD; ApoE−/− | SIRT6 | ↑Atherosclerotic lesion ↓EC-dependent vasorelaxation ↑ Unstable plaques ↑EC inflammation and monocyte adhesion |
(Z. Liu, et al., 2016) |
| JMJD1OE, JMJD1KD, balloon injury +HFD+STZ | JMJD1 | OE↑ neointimal hyperplasia KD↓ neointimal hyperplasia |
(J. Chen, et al., 2017) |
| JMJD3 Δmye+BMT (into LDLr−/−) | JMJD3 | ↑ Advanced atherosclerotic lesions ↑ Plaque necrosis -Plaque size |
(Neele, et al., 2018) |
| JMJD1KD+ balloon injury JMJD1KD+ left carotid artery partial ligation |
JMJD3 | ↓Neointimal hyperplasia ↓VSMC proliferation, migration, inflammation |
(Luo, et al., 2018) |
Abbreviations: AAA, abdominal aortic aneurysm; ABCA1, ATP binding cassette subfamily A member 1; Ang-II, angiotensin II; ApoE, apolipoprotein E; BMT, bone marrow transplantation; DNMT, DNA methyltransferase; EC, endothelial cell; eNOS, endothelial nitric oxide synthase; EZH2, enhancer of zeste homolog 2; HDAC, histone deacetylase; Hem, hematopoietic cells; HFHS, high fat high sucrose; JMJD3, JmjC domain-containing protein 3; JMJD1, JmjC domain-containing protein 1; KD, knockdown; KO, knockout; LOX-1, lectin-like oxidized LDL receptor 1; MMP, matrix metalloproteinase; NF-kB, nuclear factor-kappa B; OE, overexpression; PPAR, peroxisome proliferator-activated receptor SIRT, sirtuin; TET2, TET methylcytosine dioxygenase 2; Tg, transgene; VSMC, vascular smooth muscle cells; ΔHem, hematopoietic cell-knockout; ΔMye, myeloid cell-specific knockout; ΔVSMC, vascular smooth muscle cell-specific knockout.