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miR-29 contributes to normal endothelial function and can restore it in cardiometabolic disorders. EMBO Mol Med 2018 03;10(3)

Date

01/28/2018

Pubmed ID

29374012

Pubmed Central ID

PMC5840545

DOI

10.15252/emmm.201708046

Scopus ID

2-s2.0-85041063208   42 Citations

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.

Author List

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

Authors

Aron Geurts PhD Professor in the Physiology department at Medical College of Wisconsin
David Jensen in the CTSI department at Medical College of Wisconsin - CTSI
Alison J. Kriegel PhD Associate Professor in the Physiology department at Medical College of Wisconsin
Mingyu Liang PhD Center Director, Professor in the Physiology department at Medical College of Wisconsin
Pengyuan Liu PhD Adjunct Professor in the Physiology department at Medical College of Wisconsin
Yong Liu PhD Assistant Professor in the Physiology department at Medical College of Wisconsin
Michael E. Widlansky MD Associate Director, Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adult
Aged
Animals
Arterioles
Cardiovascular Diseases
Diabetes Mellitus, Type 2
Disease Models, Animal
Endothelium, Vascular
Gene Expression Regulation
Humans
MicroRNAs
Middle Aged
Nitric Oxide
Rats
Vascular Resistance
Vasodilation