Open AccessmiR‐29 contributes to normal endothelial function and can restore it in cardiometabolic disorders
Author(s) -
Widlansky Michael E,
Jensen David M,
Wang Jingli,
Liu Yong,
Geurts Aron M,
Kriegel Alison J,
Liu Pengyuan,
Ying Rong,
Zhang Guangyuan,
Casati Marc,
Chu Chen,
Malik Mobin,
Branum Amberly,
Tanner Michael J,
Tyagi Sudhi,
Usa Kristie,
Liang Mingyu
Publication year - 2018
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201708046
Subject(s) - function (biology) , endothelial dysfunction , medicine , microbiology and biotechnology , biology
We investigated the role of micro RNA s (mi RNA ) 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 T2 DM patients. Intraluminal delivery of miR‐29a‐3p or miR‐29b‐3p mimics restored normal endothelium‐dependent vasodilation ( EDVD ) in T2 DM 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 si RNA improved EDVD in arterioles obtained from T2 DM 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.