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. 2021 Oct 26;78(23):7355–7378. doi: 10.1007/s00018-021-03979-4

Table 2.

Use of miR-34a antagomir or mimic in experimental animal models of vascular diseases

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