Open AccessMicro RNA let‐7g possesses a therapeutic potential for peripheral artery disease
Author(s) -
Hsu PoYuan,
Hsi Edward,
Wang TzuMing,
Lin RueyTay,
Liao YiChu,
Juo SuhHang H.
Publication year - 2017
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12997
Subject(s) - therapeutic angiogenesis , angiogenesis , progenitor cell , neovascularization , vascular endothelial growth factor , cancer research , medicine , arteriogenesis , ischemia , gene isoform , microrna , critical limb ischemia , pharmacology , microbiology and biotechnology , biology , vascular disease , stem cell , vegf receptors , arterial disease , genetics , gene
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 micro RNA 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 TP 53. In addition, let‐7g affected the splicing factor SC 35 which subsequently enhanced the alternative splicing of VEGF ‐A from the anti‐angiogenic isoform VEGF ‐A 165b towards the pro‐angiogenic isoform VEGF ‐A 164a . The pleiotropic effects of let‐7g on angiogenesis imply that let‐7g may possess a therapeutic potential in ischaemic diseases.