MicroRNA let‐7g possesses a therapeutic potential for peripheral artery disease |
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| Authors: | Po‐Yuan Hsu Edward Hsi Tzu‐Ming Wang Ruey‐Tay Lin Yi‐Chu Liao Suh‐Hang H Juo |
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| Affiliation: | 1. Department of Medical Research, China Medical University Hospital, Taichung, Taiwan;2. Department of Neurology, Kaohsiung Medical University, Kaohsiung, Taiwan;3. Department of Neurology, National Yang‐Ming University School of Medicine, Taipei, Taiwan;4. Department of Neurology, Taipei Veterans General Hospital, Taipei, TaiwanThese authors contributed equally.;5. Graduate Institute of Biomedical Sciences, China Medical University, Taichung, TaiwanThese authors contributed equally. |
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| Abstract: | Peripheral artery disease (PAD) is a manifestation of systemic atherosclerosis and conveys a significant health burden globally. Critical limb ischaemia encompasses the most severe consequence of PAD. Our previous studies indicate that microRNA let‐7g prevents atherosclerosis and improves endothelial functions. This study aimed to investigate whether and how let‐7g therapy may improve blood flow to ischaemic limbs. The present study shows that let‐7g has multiple pro‐angiogenic effects on mouse ischaemic limb model and could be a potential therapeutic agent for PAD. Mice receiving intramuscular injection of let‐7g had more neovascularization, better local perfusion and increased recruitment of endothelial progenitor cells after hindlimb ischaemia. The therapeutic effects of let‐7g's on angiogenesis are mediated by multiple regulatory machinery. First, let‐7g increased expression of vascular endothelial growth factor‐A (VEGF‐A) and VEGF receptor‐2 (VEGFR‐2) through targeting their upstream regulators HIF‐3α and TP53. In addition, let‐7g affected the splicing factor SC35 which subsequently enhanced the alternative splicing of VEGF‐A from the anti‐angiogenic isoform VEGF‐A165b towards the pro‐angiogenic isoform VEGF‐A164a. The pleiotropic effects of let‐7g on angiogenesis imply that let‐7g may possess a therapeutic potential in ischaemic diseases. |
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| Keywords: | microRNA let‐7g vascular endothelial growth factor‐A endothelial progenitor cells peripheral artery disease angiogenesis |
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