Table 2.
Animal Model | miR-34a inhibitor | miR-34a mimic | Route of administration | Treatment effect | References | |
---|---|---|---|---|---|---|
HIV-1 Tat transgenicmice | Antago-miR-34a | – | Tail-vein | Beneficial: ameliorates aortic endothelial dysfunction | – | [111] |
Antiretroviral drugs (lopinavir/ritonavir)-treated mice | Antago-miR-34a | – | Tail-vein | Beneficial: ameliorates aortic endothelial dysfunction | – | [111] |
Vit D-treated Mir34a−/− mice | Genetic global ablation | – |
Beneficial: reduces soft tissue and aorta calcification; it decreases vascular inflammation |
– | [35, 42] | |
HFD-treated ApoE−/– mice | Antago-miR-34a | – | Tail-vein | Beneficial: abates aortic atherosclerotic plaque lesion development | – | [149] |
Femoral artery denudation injury mice | Ago-miR-34a | Perivascular delivery | Beneficial: prevents neointima formation | – | [155] | |
Western diet fed Ldlr–/– or ApoE–/– mice | Hepatic overexpression of miR-34a by an adenovirus | Detrimental: causes liver steatosis. Protective: atheroprotective | [157] | |||
HFD-treated Mir34a macrophage-specific or global ablation in Ldlr-/- or ApoE-/- mice | Beneficial: improves dyslipidemia, reduces atherosclerosis, obesity and NAFLD | [144] | ||||
HFD-treated Ldlr-/- or ApoE-/- mice | LNA miR-34a inhibitor | Systemic | Beneficial: improves dyslipidemia, obesity and NAFLD and reduces atherosclerosis | [144] | ||
AAA induced by Ang II infusion in ApoE-/- mice | AAV9-anti-miR-34a | AAV9-miR-34a | Systemic | Beneficial: Inhibits Ang II-induced AAA formation, vascular senescence and inflammation | Detrimental: Exacerbates Ang II-induced AAA formation, vascular senescence and inflammation | [167] |
Hypoxia-induced PAH in rats | miR-34a mimic | Intratracheal nebulization | Prevention of hypoxia-induced pulmonary hypertension and pulmonary vascular remodeling | [173] | ||
Type 2 diabetes db/db mice and STZ-induced type 1 diabetes in mice | LNA miR-34a inhibitor | Systemic | Beneficial: preserves endothelium-dependent vasorelaxation without affecting the hyperglycemic status | [195] | ||
Endothelial miR-34a knockout mice | Beneficial: preserves endothelium-dependent vasorelaxation without affecting the hyperglycemic status | [195] | ||||
STZ-induced type 1 diabetes in mice | Antago-miR-34a | Subcutaneous injection once a week for 24 weeks | Beneficial: mitigates tunica media thickness and impaired contraction and relaxation | [194] |
AAA abdominal aortic aneurism, AAV9 adeno-associated Virus Serotype 9, Ang II Angiotensin II; ApoE Apolipoprotein E, HFD high-fat diet, HIV human immunodeficiency virus, LNA locked nucleic acid, Ldlr low-density lipoprotein receptor, NAFLD non-alcoholic fatty liver disease, PAH pulmonary arterial hypertension, ST streptozotocin, Vit D Vitamin D