miR-29 contributes to normal endothelial function and can restore it in
cardiometabolic disorders.
Authors Widlansky ME, Jensen DM, Wang J, Liu Y, Geurts AM, Kriegel AJ, Liu P, Ying R,
Zhang G, Casati M, Chu C, Malik M, Branum A, Tanner MJ, Tyagi S, Usa K, Liang M
Submitted By Mingyu Liang on 2/20/2018
Status Published
Journal EMBO molecular medicine
Year 2018
Date Published 1/1/2018
Volume : Pages Not Specified : Not Specified
PubMed Reference 29374012
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
ofMir29b-1/agene in rats led to impaired EDVD and exacerbation of hypertension
in the rats. miR-29b-3p mimic increased, while anti-miR-29b-3p orMir29b-1/agene
mutation decreased, nitric oxide levels in arterioles. The mutation
ofMir29b-1/agene 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
orMir29b-1/amutant 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.

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