BACKGROUND: Dysfunction of circulating endothelial progenitor cells (EPCs) is associated with the onset of cardiovascular disorders. Circulating microRNAs (miRNAs) have been recognized as novel biomarkers and potential therapeutic targets. Here, we examined the role of miR-26a overexpression in atherosclerosis and explored the underlying mechanisms. METHODS: EPCs were obtained from patients with atherosclerosis and healthy controls. Bone marrow (BM)-derived EPCs were exposed to hypoxia to mimic the atherosclerotic environment and miR-26a, EphA2 and p38 MAPK levels were measured by qRT-PCR and western blotting, and VEGF levels were determined by enzyme linked immunosorbent assay. Cell viability was assessed using the MTT assay, and luciferase activity assays confirmed EphA2 as a target of miR-26a. RESULTS: MiR-26a was overexpressed in patients with atherosclerosis and associated with EPC dysfunction. EphA2 was identified as a direct target of miR-26a. Overexpression of miR-26a downregulated EphA2 and impaired EPC function, whereas knockdown of miR-26a upregulated EphA2 and reversed hypoxia-induced EPC dysfunction. MiR-26a overexpression or knockdown modulated the activity of p38 MAPK and the levels of VEGF in EPCs. CONCLUSIONS: The role of miR-26a in atherosclerosis is mediated by its target EphA2 via a mechanism involving the p38 MAPK/VEGF pathway.
BACKGROUND: Dysfunction of circulating endothelial progenitor cells (EPCs) is associated with the onset of cardiovascular disorders. Circulating microRNAs (miRNAs) have been recognized as novel biomarkers and potential therapeutic targets. Here, we examined the role of miR-26a overexpression in atherosclerosis and explored the underlying mechanisms. METHODS: EPCs were obtained from patients with atherosclerosis and healthy controls. Bone marrow (BM)-derived EPCs were exposed to hypoxia to mimic the atherosclerotic environment and miR-26a, EphA2 and p38 MAPK levels were measured by qRT-PCR and western blotting, and VEGF levels were determined by enzyme linked immunosorbent assay. Cell viability was assessed using the MTT assay, and luciferase activity assays confirmed EphA2 as a target of miR-26a. RESULTS:MiR-26a was overexpressed in patients with atherosclerosis and associated with EPC dysfunction. EphA2 was identified as a direct target of miR-26a. Overexpression of miR-26a downregulated EphA2 and impaired EPC function, whereas knockdown of miR-26a upregulated EphA2 and reversed hypoxia-induced EPC dysfunction. MiR-26a overexpression or knockdown modulated the activity of p38 MAPK and the levels of VEGF in EPCs. CONCLUSIONS: The role of miR-26a in atherosclerosis is mediated by its target EphA2 via a mechanism involving the p38 MAPK/VEGF pathway.
Authors: Ryan J Good; Laura Hernandez-Lagunas; Ayed Allawzi; Joanne K Maltzahn; Christine U Vohwinkel; Arun K Upadhyay; Uday B Kompella; Konstantin G Birukov; Todd C Carpenter; Carmen C Sucharov; Eva Nozik-Grayck Journal: Am J Physiol Lung Cell Mol Physiol Date: 2018-07-19 Impact factor: 5.464
Authors: Muralidharan Jayaraman; Rangasudhagar Radhakrishnan; Cara A Mathews; Mingda Yan; Sanam Husain; Katherine M Moxley; Yong Sang Song; Danny N Dhanasekaran Journal: Genes Cancer Date: 2017-05
Authors: Lingshang Kong; Nan Hu; Xiaolong Du; Wenbin Wang; Hong Chen; Wendong Li; Sen Wei; Hao Zhuang; Xiaoqiang Li; Chenglong Li Journal: J Transl Med Date: 2016-01-22 Impact factor: 5.531