| Role of miR-195 in Aortic Aneurysmal Disease. | |
MedLine Citation:
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PMID: 25201911 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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:
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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:
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Type: JOURNAL ARTICLE Date: 2014-9-8 |
Journal Detail:
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Title: Circulation research Volume: - ISSN: 1524-4571 ISO Abbreviation: Circ. Res. Publication Date: 2014 Sep |
Date Detail:
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Created Date: 2014-9-9 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0047103 Medline TA: Circ Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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