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EMBO Mol Med. 2018 Mar;10(3). pii: e8046. doi: 10.15252/emmm.201708046.

miR-29 contributes to normal endothelial function and can restore it in cardiometabolic disorders.

Author information

1
Division of Cardiovascular Medicine, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA mwidlans@mcw.edu mliang@mcw.edu.
2
Department of Physiology, Center of Systems Molecular Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
3
Division of Cardiovascular Medicine, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
4
Department of Physiology, Center of Systems Molecular Medicine, Medical College of Wisconsin, Milwaukee, WI, USA mwidlans@mcw.edu mliang@mcw.edu.

Abstract

We investigated the role of microRNAs (miRNA) in endothelial dysfunction in the setting of cardiometabolic disorders represented by type 2 diabetes mellitus (T2DM). miR-29 was dysregulated in resistance arterioles obtained by biopsy in T2DM patients. Intraluminal delivery of miR-29a-3p or miR-29b-3p mimics restored normal endothelium-dependent vasodilation (EDVD) in T2DM arterioles that otherwise exhibited impaired EDVD Intraluminal delivery of anti-miR-29b-3p in arterioles from non-DM human subjects or rats or targeted mutation of Mir29b-1/a gene in rats led to impaired EDVD and exacerbation of hypertension in the rats. miR-29b-3p mimic increased, while anti-miR-29b-3p or Mir29b-1/a gene mutation decreased, nitric oxide levels in arterioles. The mutation of Mir29b-1/a gene led to preferential differential expression of genes related to nitric oxide including Lypla1. Lypla1 was a direct target of miR-29 and could abrogate the effect of miR-29 in promoting nitric oxide production. Treatment with Lypla1 siRNA improved EDVD in arterioles obtained from T2DM patients or Mir29b-1/a mutant rats or treated with anti-miR-29b-3p. These findings indicate miR-29 is required for normal endothelial function in humans and animal models and has therapeutic potential for cardiometabolic disorders.

KEYWORDS:

diabetes; endothelium; hypertension; microRNA; nitric oxide

PMID:
29374012
PMCID:
PMC5840545
DOI:
10.15252/emmm.201708046
[Indexed for MEDLINE]
Free PMC Article

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