Abstract 16010: Reduced Expression of miR-130a-3p Contributes to Endothelial Cell Senescence and Age-dependent Impairment of Neovascularization
Background: Aging, a major cardiovascular risk factor, is also associated with impaired neovascularization in response to ischemia. Micro RNAs (miRNAs) are small noncoding RNAs emerging as key regulators of several physiological and pathological processes. Here we investigated the potential role of miRNAs in endothelial cell senescence and age-dependent impairment of neovascularization.
Methods/Results: Mouse aortic endothelial cells (MAECs) were isolated from young (2 months old) and old (15 months old) C57Bl/6 mice. In other experiments, low passage (young) human umbilical vein endothelial cells (HUVECs) were compared to high passage (old) HUVECs. Next generation sequencing and qRT-PCR analyses identified miR-130a-3p as a pro-angiogenic miRNA which expression is significantly reduced in old vs young endothelial cells (ECs). Transfection of young ECs with a miR-130a-3p inhibitor led to accelerated senescence (β-Galactosidase assay) and impaired EC angiogenic functions including migration, proliferation and tube formation. Conversely, forced expression of miR-130a-3p in old ECs reduced senescence and improved EC angiogenic functions. In a mouse model of hindlimb ischemia, intramuscular injection of a miR-130a-3p mimic in older mice restored blood flow recovery (Laser Doppler imaging) and vascular densities in ischemic muscles (CD31 immunostaining), improved functional mobility and reduced tissue damages. Interestingly, forced expression of miR-130a-3p in older mice was also associated with a significant increase in the number of bone marrow-derived pro-angiogenic cells (PACs) after ischemia. Moreover, the functional activities of PACs (migration, adhesion to an endothelial monolayer and integration into tubular networks) were all improved in older mice treated with miR-130a-3p mimic compared to those treated with a miR mimic control.
Conclusions: Decreased expression of miR-130a-3p contributes to endothelial cell senescence and age-dependent impairment of neovascularization. Forced expression of miR-130a-3p using a miRNA mimic could constitute a novel therapeutic strategy to improve blood flow recovery and reduce tissue ischemia in older patients with severe ischemic vascular diseases.
Author Disclosures: W. Dhahri: None. S. Dussault: None. M. Desjarlais: None. R. Mathieu: None. A. Rivard: None.
- © 2016 by American Heart Association, Inc.