Format

Send to

Choose Destination
EMBO Mol Med. 2016 Jun 1;8(6):643-53. doi: 10.15252/emmm.201506031. Print 2016 Jun.

Chronic miR-29 antagonism promotes favorable plaque remodeling in atherosclerotic mice.

Author information

1
Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA Department of Pharmacology, School of Medicine Yale University, New Haven, CT, USA.
2
Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA Integrative Cell Signaling and Neurobiology of Metabolism Program, Section of Comparative Medicine and Department of Pathology, School of Medicine Yale University, New Haven, CT, USA.
3
King's British Heart Foundation Centre, King's College London, London, UK.
4
Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA Department of Cardiology, School of Medicine Yale University, New Haven, CT, USA.
5
miRagen Therapeutics, Boulder, CO, USA.
6
Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Hannover, Germany National Heart and Lung Institute, Imperial College London, London, UK.
7
Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA Department of Pharmacology, School of Medicine Yale University, New Haven, CT, USA william.sessa@yale.edu.

Abstract

Abnormal remodeling of atherosclerotic plaques can lead to rupture, acute myocardial infarction, and death. Enhancement of plaque extracellular matrix (ECM) may improve plaque morphology and stabilize lesions. Here, we demonstrate that chronic administration of LNA-miR-29 into an atherosclerotic mouse model improves indices of plaque morphology. This occurs due to upregulation of miR-29 target genes of the ECM (col1A and col3A) resulting in reduced lesion size, enhanced fibrous cap thickness, and reduced necrotic zones. Sustained LNA-miR-29 treatment did not affect circulating lipids, blood chemistry, or ECM of solid organs including liver, lung, kidney, spleen, or heart. Collectively, these data support the idea that antagonizing miR-29 may promote beneficial plaque remodeling as an independent approach to stabilize vulnerable atherosclerotic lesions.

KEYWORDS:

LNA; atherosclerosis; miR‐29; plaque; stability

PMID:
27137489
PMCID:
PMC4888854
DOI:
10.15252/emmm.201506031
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center