Role of miR-195 in aortic aneurysmal disease

Anna Zampetaki*, Rizwan Q Attia, Ursula Mayr, Renata S Gomes, Alkystis Phinikaridou, Xiaoke Yin, Sarah Langley, Peter Willeit, Ruifang Lu, Bruce Fanshawe, Marika Fava, Javier Barallobre-Barreiro, Chris Molenaar, Po-Wah So, Abeera Abbas, Marjan Jahangiri, Matthew Waltham, René Botnar, Alberto Smith, Manuel Mayr

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

92 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)857-866
Number of pages10
JournalCirculation Research
Volume115
Issue number10
Early online date8 Sept 2014
DOIs
Publication statusPublished - 24 Oct 2014

Keywords

  • Aneurysm
  • Biological markers
  • Extracellular matrix
  • microRNAs
  • Myocytes, smooth muscle

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