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Role of miR-195 in Aortic Aneurysmal Disease.
MedLine Citation:
PMID:  25201911     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Rationale: Abdominal aortic aneurysms (AAA) 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: 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 upon angiotensin II infusion. Proteomics analysis of the secretome of murine aortic smooth muscle cells, following 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 to 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 aneurysm formation. 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 AAA 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 AAA suggesting that miRNAs might serve as a noninvasive biomarker of AAA.
Authors:
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
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-9-8
Journal Detail:
Title:  Circulation research     Volume:  -     ISSN:  1524-4571     ISO Abbreviation:  Circ. Res.     Publication Date:  2014 Sep 
Date Detail:
Created Date:  2014-9-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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