MicroRNA-29 in aortic dilation: Implications for aneurysm formation

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

Research output: Contribution to journalArticle

Abstract

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 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.

Original languageEnglish
Pages (from-to)1115-1119
Number of pages5
JournalCirculation Research
Volume109
Issue number10
DOIs
Publication statusPublished - Oct 28 2011

    Fingerprint

Keywords

  • aging
  • aneurysm
  • microRNA

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Boon, R. A., Seeger, T., Heydt, S., Fischer, A., Hergenreider, E., Horrevoets, A. J. G., Vinciguerra, M., Rosenthal, N., Sciacca, S., Pilato, M., Van Heijningen, P., Essers, J., Brandes, R. P., Zeiher, A. M., & Dimmeler, S. (2011). MicroRNA-29 in aortic dilation: Implications for aneurysm formation. Circulation Research, 109(10), 1115-1119. https://doi.org/10.1161/CIRCRESAHA.111.255737