Role of miR-195 in aortic aneurysmal disease.

Zampetaki, Anna, Attia, Rizwan, Mayr, Ursula, Gomes, Renata S.M., Phinikaridou, Alkystis, Yin, Xiaoke, Langley, Sarah R. ORCID: https://orcid.org/0000-0003-4419-476X, Willeit, Peter, Lu, Ruifang, Fanshawe, Bruce, Fava, Marika, Barallobre-Barreiro, Javier, Molenaar, Chris, So, Po-Wah, Abbas, Abeera, Jahangiri, Marjan, Waltham, Matthew, Botnar, Rene, Smith, Alberto and Mayr, Manuel 2014. Role of miR-195 in aortic aneurysmal disease. Circulation Research 115 (10) , pp. 857-866. 10.1161/circresaha.115.304361

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Publisher:	American Heart Association
ISSN:	0009-7330
Date of Acceptance:	8 September 2014
Last Modified:	06 Sep 2023 07:15
URI:	https://orca.cardiff.ac.uk/id/eprint/162127

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