MiR-216a: a link between endothelial dysfunction and autophagy.
Menghini R1, Casagrande V1, Marino A1, Marchetti V1, Cardellini M1, Stoehr R1, Rizza S1, Martelli E2, Greco S3, Mauriello A2, Ippoliti A2, Martelli F3, Lauro R1, Federici M1.
Cell Death Dis.
Cells used in publication:
Endothelial, umbilical vein, human (HUVEC)
Tissue Origin: vein
Endothelial, coronary art, human (HCAEC)
Tissue Origin: artery
Endothelial, aortic, human (HAEC)
Tissue Origin: aortic
Endothelial Cell Growth Medium 2
Endothelial Cell Growth Medium-2 Microvascular
Endothelial dysfunction and impaired autophagic activity have a crucial role in aging-related diseases such as cardiovascular dysfunction and atherosclerosis. We have identified miR-216a as a microRNA that is induced during endothelial aging and, according to the computational analysis, among its targets includes two autophagy-related genes, Beclin1 (BECN1) and ATG5. Therefore, we have evaluated the role of miR-216a as a molecular component involved in the loss of autophagic function during endothelial aging. The inverse correlation between miR-216a and autophagic genes was conserved during human umbilical vein endothelial cells (HUVECs) aging and in vivo models of human atherosclerosis and heart failure. Luciferase experiments indicated BECN1, but not ATG5 as a direct target of miR-216a. HUVECs were transfected in order to modulate miR-216a expression and stimulated with 100?µg/ml oxidized low-density lipoprotein (ox-LDL) to induce a stress repairing autophagic process. We found that in young HUVECs, miR-216a overexpression repressed BECN1 and ATG5 expression and the ox-LDL induced autophagy, as evaluated by microtubule-associated protein 1 light chain 3 (LC3B) analysis and cytofluorimetric assay. Moreover, miR-216a stimulated ox-LDL accumulation and monocyte adhesion in HUVECs. Conversely, inhibition of miR-216a in old HUVECs rescued the ability to induce a protective autophagy in response to ox-LDL stimulus. In conclusion, mir-216a controls ox-LDL induced autophagy in HUVECs by regulating intracellular levels of BECN1 and may have a relevant role in the pathogenesis of cardiovascular disorders and atherosclerosis.
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