Abstract 15036: Role of miR-195 in Aneurysm Formation
Introduction: Abdominal aortic aneurysm (AAA) is a degenerative disease of the aorta. Apart from the miR-29 family, miR-195 has been implicated in the regulation of the vascular extracellular matrix (ECM). Our aim was to assess the effect of the miR-15 family in aneurysm formation.
Methods and Results: Expression of the miR-15 and miR-29 families was assessed in human aortic tissue. In human aneurysmal tissue, miR-195 expression was reduced to the same extent as miR-29b. In plasma, an inverse correlation of miR-195 was observed with the presence of AAA and aortic diameter. To evaluate the effect of miR-195 in ECM deposition, proteomics analysis was performed on the secretome of murine aortic smooth muscle cells (SMCs) following miRNA manipulation. MiR-195 targeted a cadre of ECM proteins, including collagens, proteoglycans, elastin and proteins associated with elastic microfibrils, albeit miR-29b showed a stronger effect. Systemic administration of cholesterol bound antagomiRs revealed better targeting efficacy of miR-195 compared to miR-29b in the uninjured aorta. A significant increase in aortic elastin expression was observed in wildtype animals injected with antagomiR-195. Yet, in apolipoprotein E-deficient mice receiving angiotensin II, inhibition of miR-29b but not miR-195 led to a significant inhibition of aortic aneurysm formation.
Conclusions: We provide the first evidence that miR-195 may contribute to the pathogenesis of aneurysmal disease. Levels of miR-195 were reduced in human aneurysmal tissue and in plasma of patients with AAA. Although, miR-195 emerged as a potent regulator of aortic ECM, its inhibition was less effective than miR-29b in preventing aneurysm formation in preclinical models.
Author Disclosures: A. Zampetaki: None. R. Attia: None. U. Mayr: None. R. Gomes: None. A. Phinikaridou: None. X. Yin: None. S. Lnagley: None. P. Willeit: None. B. Fanshawe: None. M. Fava: None. J. Barallobre Barreiro: None. P. So: None. A. Abbas: None. M. Jahangiri: None. M. Waltham: None. R. Botnar: None. A. Smith: None. M. Mayr: None.
- © 2014 by American Heart Association, Inc.