Protective effects of let-7a and let-7b on oxidized low-density lipoprotein induced endothelial cell injuries

• Published in: PloS one 2014-09, Vol.9 (9), p.e106540-e106540
• Main Authors: Bao, Mei-Hua, Zhang, Yi-Wen, Lou, Xiao-Ya, Cheng, Yu, Zhou, Hong-Hao
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions; Apoptosis; Arteriosclerosis; Atherogenesis; Atherosclerosis; Binding Sites; Biology and Life Sciences; Cardiovascular disease; Cardiovascular diseases; Cardiovascular system; Density; Dephosphorylation; Endothelial cells; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Endothelium; Gene expression; Glucose; HEK293 Cells; Hospitals; Human Umbilical Vein Endothelial Cells; Humans; Inhibition; Kinases; Laboratories; Lectins; Lipoproteins; Lipoproteins, LDL - pharmacology; Liquid oxygen; Low density lipoproteins; LOX-1 protein; MAP Kinase Signaling System - drug effects; Medicine and Health Sciences; MicroRNA; MicroRNAs; MicroRNAs - metabolism; miRNA; NF-κB protein; Nitric oxide; Nitric Oxide Synthase Type III - metabolism; Nitric-oxide synthase; Nuclear transport; Overexpression; Pathogenesis; Pharmacology; Phosphorylation; Plasmids; Polyclonal antibodies; Post-transcription; Reactive Oxygen Species - metabolism; Receptor density; Ribonucleic acid; RNA; Rodents; Scavenger Receptors, Class E - genetics; Scavenger Receptors, Class E - metabolism; Translocation
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0106540

Lectin-like low-density lipoprotein receptor 1 (LOX-1) is a receptor for oxidized low density lipoprotein (oxLDL) in endothelial cells. The activation of LOX-1 by oxLDL stimulates the apoptosis and dysfunction of endothelial cells, and contributes to atherogenesis. However, the regulatory factors for LOX-1 are still unclear. MicroRNAs are small, endogenous, non-coding RNAs that regulate gene expressions at a post-transcriptional level. The let-7 family is the second microRNA been discovered, which plays important roles in cardiovascular diseases. Let-7a and let-7b were predicted to target LOX-1 3'-UTR and be highly expressed in endothelial cells. The present study demonstrated that LOX-1 was a target of let-7a and let-7b. They inhibited the expression of LOX-1 by targeting the positions of 310-316 in LOX-1 3'-UTR. Over-expression of let-7a and let-7b inhibited the oxLDL-induced endothelial cell apoptosis, NO deficiency, ROS over-production, LOX-1 upregulation and endothelial nitric oxide synthase (eNOS) downregulation. Moreover, we found that oxLDL treatment induced p38MAPK phosphorylation, NF-κB nuclear translocation, IκB degradation and PKB dephosphorylation. Let-7a or let-7b over-expression attenuated these alterations significantly. The present study may provide a new insight into the protective properties of let-7a and let-7b in preventing the endothelial dysfunction associated with cardiovascular disease, such as atherosclerosis.