MicroRNA-145 Mediates the Formation of Angiotensin II-Induced Murine Abdominal Aortic Aneurysm.

Abstract

BACKGROUND:

MicroRNA-145 (miR-145) has been implicated in vascular smooth muscle cell differentiation, but the underlying mechanisms have not been fully understood, especially their role in abdominal aortic aneurysm (AAA) expansion. Here, we sought to explore and define the mechanisms of miR-145 function in the experimental AAA models in AngII-infused ApoE-/- mice.

METHODS:

miR-145 was overexpressed in ApoE-/- mice via lentivirus infection, and then the incidence of AAA, maximum abdominal aortic diameter, elastin degradation and MMP2 activation were determined in AngII-infused ApoE-/- mice.

RESULTS:

In vivo overexpression of miR-145 by lentivirus infection greatly decreased the incidence of AAA, maximum abdominal aortic diameter, and elastin degradation, accompanied with downregulation of MMP2 activation in AngII-infused ApoE-/- mice. Cell culture assays indicated that miR-145 inhibited AngII-induced upregulation of MMP2 gene expression. In contrast, deficiency of MMP2 abolished the effects of miR-145 on AngII-induced elastin and collagens degradations in ApoE-/- mice.

CONCLUSION:

These data suggest that regulation of expression of miR-145 may be a potential therapeutic option for vascular disease progression such as AAA expansion.

• Authors: Jing Wu, Jun Wang, Xiaoou Li, Xiaofeng Liu, Xiuyan Yu, Yunling Tian
• Journal: Heart, lung & circulation (Heart Lung Circ) Vol. 26 Issue 6 Pg. 619-626 (Jun 2017) ISSN: 1444-2892 [Electronic] Australia
• PMID: 27956160 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Chemical References

• Apolipoproteins E
• MIRN145 microRNA, mouse
• MicroRNAs
• Angiotensin II
• Collagen
• Elastin
• Matrix Metalloproteinase 2
• Mmp2 protein, mouse

Topics

• Angiotensin II (adverse effects, pharmacology)
• Animals
• Aortic Aneurysm, Abdominal (chemically induced, genetics, metabolism, physiopathology)
• Apolipoproteins E (deficiency, metabolism)
• Collagen (genetics, metabolism)
• Disease Models, Animal
• Elastin (genetics, metabolism)
• Gene Expression Regulation, Enzymologic
• Lentivirus
• Matrix Metalloproteinase 2 (biosynthesis, genetics)
• Mice
• Mice, Knockout
• MicroRNAs (biosynthesis, genetics)
• Transduction, Genetic
• Up-Regulation