Format

Send to

Choose Destination
Circ Res. 2014 Oct 24;115(10):857-66. doi: 10.1161/CIRCRESAHA.115.304361. Epub 2014 Sep 8.

Role of miR-195 in aortic aneurysmal disease.

Author information

1
From the King's British Heart Foundation Centre (A.Z., R.A., U.M., R.S.M.G., A.P., X.Y., S.R.L., R.L., B.F., M.F., J.B.-B., C.M., A.A., M.W., R.B., A.S., M.M.) and Institute of Psychiatry (P.-W.S.), King's College London, United Kingdom; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.); and Department of Cardiac Surgery, St George's Healthcare NHS Trust, London, United Kingdom (M.F., M.J.). anna.zampetaki@kcl.ac.uk manuel.mayr@kcl.ac.uk.
2
From the King's British Heart Foundation Centre (A.Z., R.A., U.M., R.S.M.G., A.P., X.Y., S.R.L., R.L., B.F., M.F., J.B.-B., C.M., A.A., M.W., R.B., A.S., M.M.) and Institute of Psychiatry (P.-W.S.), King's College London, United Kingdom; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.); and Department of Cardiac Surgery, St George's Healthcare NHS Trust, London, United Kingdom (M.F., M.J.).

Abstract

RATIONALE:

Abdominal aortic aneurysms constitute a degenerative process in the aortic wall. Both the miR-29 and miR-15 families have been implicated in regulating the vascular extracellular matrix.

OBJECTIVE:

Our aim was to assess the effect of the miR-15 family on aortic aneurysm development.

METHODS AND RESULTS:

Among the miR-15 family members, miR-195 was differentially expressed in aortas of apolipoprotein E-deficient mice on angiotensin II infusion. Proteomics analysis of the secretome of murine aortic smooth muscle cells, after miR-195 manipulation, revealed that miR-195 targets a cadre of extracellular matrix proteins, including collagens, proteoglycans, elastin, and proteins associated with elastic microfibrils, albeit miR-29b showed a stronger effect, particularly in regulating collagens. Systemic and local administration of cholesterol-conjugated antagomiRs revealed better inhibition of miR-195 compared with miR-29b in the uninjured aorta. However, in apolipoprotein E-deficient mice receiving angiotensin II, silencing of miR-29b, but not miR-195, led to an attenuation of aortic dilation. Higher aortic elastin expression was accompanied by an increase of matrix metalloproteinases 2 and 9 in mice treated with antagomiR-195. In human plasma, an inverse correlation of miR-195 was observed with the presence of abdominal aortic aneurysms and aortic diameter.

CONCLUSIONS:

We provide the first evidence that miR-195 may contribute to the pathogenesis of aortic aneurysmal disease. Although inhibition of miR-29b proved more effective in preventing aneurysm formation in a preclinical model, miR-195 represents a potent regulator of the aortic extracellular matrix. Notably, plasma levels of miR-195 were reduced in patients with abdominal aortic aneurysms suggesting that microRNAs might serve as a noninvasive biomarker of abdominal aortic aneurysms.

KEYWORDS:

aneurysm; biological markers; extracellular matrix; microRNAs; myocytes, smooth muscle

PMID:
25201911
DOI:
10.1161/CIRCRESAHA.115.304361
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center