MicroRNA-145 Mediates the Formation of Angiotensin II-Induced Murine Abdominal Aortic Aneurysm

Background MicroRNA-145 (miR-145) has been implicated in vascular smooth muscle cell differentiation, but the underlying mechanisms have not been fully understood, especially their role in abdominal aortic aneurysm (AAA) expansion. Here, we sought to explore and define the mechanisms of miR-145 function in the experimental AAA models in AngII-infused ApoE(-/-) mice. Methods miR-145 was overexpressed in ApoE(-/-) mice via lentivirus infection, and then the incidence of AAA, maximum abdominal aortic diameter, elastin degradation and MMP2 activation were determined in AngII-infused ApoE(-/-) mice. Results In vivo overexpression of miR-145 by lentivirus infection greatly decreased the incidence of AAA, maximum abdominal aortic diameter, and elastin degradation, accompanied with downregulation of MMP2 activation in AngII-infused ApoE(-/-) mice. Cell culture assays indicated that miR-145 inhibited AngII-induced upregulation of MMP2 gene expression. In contrast, deficiency of MMP2 abolished the effects of miR-145 on AngII-induced elastin and collagens degradations in ApoE(-/-) mice. Conclusion These data suggest that regulation of expression of miR-145 may be a potential therapeutic option for vascular disease progression such as AAA expansion.