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Nat Commun. 2014 Oct 31;5:5214. doi: 10.1038/ncomms6214.

miR-24 limits aortic vascular inflammation and murine abdominal aneurysm development.

Author information

1
1] Division of Cardiovascular Medicine, Stanford University, Falk CVRB, 300 Pasteur Drive, Stanford, California 94305, USA [2] Center for Molecular Medicine L8:03, Department of Medicine, Karolinska Institute and University Hospital, Stockholm 17176, Sweden.
2
1] Division of Cardiovascular Medicine, Stanford University, Falk CVRB, 300 Pasteur Drive, Stanford, California 94305, USA [2] VA Palo Alto Health Care System, 3801 Miranda Avenue, Palo Alto, California 94304, USA.
3
Division of Cardiovascular Medicine, Stanford University, Falk CVRB, 300 Pasteur Drive, Stanford, California 94305, USA.
4
Center for Molecular Medicine L8:03, Department of Medicine, Karolinska Institute and University Hospital, Stockholm 17176, Sweden.
5
Center of Medical Innovation and Translational Research, Department of Clinical Gene Therapy, Osaka University, 2-2 Yamada-oka, Osaka 565-0871, Japan.
6
Center for Molecular Medicine L8:03, Department of Molecular Medicine and Surgery, Karolinska Institute and University Hospital, Stockholm 17176, Sweden.
7
Transplant and Stem Cell Immunology Laboratory, University Heart Center Hamburg, Martinistraße 52, Hamburg 20246, Germany.
8
Division of Vascular Surgery, Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA.

Abstract

Identification and treatment of abdominal aortic aneurysm (AAA) remain among the most prominent challenges in vascular medicine. MicroRNAs (miRNAs) are crucial regulators of cardiovascular pathology and represent intriguing targets to limit AAA expansion. Here we show, by using two established murine models of AAA disease along with human aortic tissue and plasma analysis, that miR-24 is a key regulator of vascular inflammation and AAA pathology. In vivo and in vitro studies reveal chitinase 3-like 1 (Chi3l1) to be a major target and effector under the control of miR-24, regulating cytokine synthesis in macrophages as well as their survival, promoting aortic smooth muscle cell migration and cytokine production, and stimulating adhesion molecule expression in vascular endothelial cells. We further show that modulation of miR-24 alters AAA progression in animal models, and that miR-24 and CHI3L1 represent novel plasma biomarkers of AAA disease progression in humans.

PMID:
25358394
PMCID:
PMC4217126
DOI:
10.1038/ncomms6214
[Indexed for MEDLINE]
Free PMC Article

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