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MicroRNA let-7g possesses a therapeutic potential for peripheral artery disease.

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-3? 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-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.

SUBMITTER: Hsu PY

PROVIDER: S-EPMC5323674 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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MicroRNA let-7g possesses a therapeutic potential for peripheral artery disease.

Hsu Po-Yuan PY Hsi Edward E Wang Tzu-Ming TM Lin Ruey-Tay RT Liao Yi-Chu YC Juo Suh-Hang H SH

Journal of cellular and molecular medicine 20161003 3

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 ...[more]

PMID: 27696675

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MicroRNA let-7g possesses a therapeutic potential for peripheral artery disease.

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MicroRNA let-7g possesses a therapeutic potential for peripheral artery disease.

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