Document Detail


MicroRNA-29 in Aortic Dilation: Implications for Aneurysm Formation.
MedLine Citation:
PMID:  21903938     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Rationale:Aging represents a major risk factor for coronary artery disease and aortic aneurysm formation. MicroRNAs (miRs) have emerged as key regulators of biological processes, but their role in age-associated vascular pathologies is unknown.Objective:We aim to identify miRs in the vasculature that are regulated by age and play a role in age-induced vascular pathologies.Methods and Results:Expression profiling of aortic tissue of young versus old mice identified several age-associated miRs. Among the significantly regulated miRs, the increased expression of miR-29 family members was associated with a profound downregulation of numerous extracellular matrix (ECM) components in aortas of aged mice, suggesting that this miR family contributes to ECM loss, thereby sensitizing the aorta for aneurysm formation. Indeed, miR-29 expression was significantly induced in 2 experimental models for aortic dilation: angiotensin II-treated aged mice and genetically induced aneurysms in Fibulin-4(R/R) mice. More importantly, miR-29b levels were profoundly increased in biopsies of human thoracic aneurysms, obtained from patients with either bicuspid (n=79) or tricuspid aortic valves (n=30). Finally, LNA-modified antisense oligonucleotide-mediated silencing of miR-29 induced ECM expression and inhibited angiotensin II-induced dilation of the aorta in mice.Conclusion:In conclusion, miR-29-mediated downregulation of ECM proteins may sensitize the aorta to the formation of aneurysms in advanced age. Inhibition of miR-29 in vivo abrogates aortic dilation in mice, suggesting that miR-29 may represent a novel molecular target to augment matrix synthesis and maintain vascular wall structural integrity.
Authors:
Reinier A Boon; Timon Seeger; Susanne Heydt; Ariane Fischer; Eduard Hergenreider; Anton J G Horrevoets; Manlio Vinciguerra; Nadia Rosenthal; Sergio Sciacca; Michele Pilato; Paula van Heijningen; Jeroen Essers; Ralf P Brandes; Andreas M Zeiher; Stefanie Dimmeler
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-9-8
Journal Detail:
Title:  Circulation research     Volume:  -     ISSN:  1524-4571     ISO Abbreviation:  -     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-9-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Institute for Cardiovascular Regeneration, Center of Molecular Medicine; the Department of Cardiology, Internal Medicine III, Goethe University, Frankfurt, Germany; the Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, the Netherlands; the European Molecular Biology Laboratory, Monterotondo, Italy; the Heart Science Centre, National Heart and Lung Institute, Imperial College, London, United Kingdom; the Australian Regenerative Medicine Institute/EMBL Australia, Monash University, Melbourne, Australia; the Mediterranean Institute for Transplantation and Advanced Specialized Therapies, Palermo, Italy; the Department of Cell Biology and Genetics, Cancer Genomics Center, Department of Radiation Oncology, Department of Vascular Surgery, Erasmus Medical Center, Rotterdam, the Netherlands; and the Institute for Cardiovascular Physiology, Goethe University, Frankfurt, Germany.
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