The development of effective pharmacological treatment of abdominal aortic aneurysm (AAA) potentially offers great benefit to patients with pre-aneurysmal aortic dilation by slowing the expansion of aneurysms and reducing the need for surgery. To date, therapeutic targets for slowing aortic dilation have had low efficacy. Thus, in this study, we aim to elucidate possible mechanisms driving aneurysm progression in order to identify potential targets for pharmacological intervention. We demonstrate that mTOR signaling is over activated in aortic smooth muscle cells (SMCs) which contributes to murine AAA. Rapamycin, a typical mTOR pathway inhibitor, dramatically limits the expansion of the abdominal aorta following intraluminal elastase perfusion. Furthermore, reduction of aortic diameter is achieved by inhibition of the mTOR pathway, which preserves and/or restores the contractile phenotype of SMCs and downregulates macrophage infiltration, MMPs expression, and inflammatory cytokine production. Taken together, these results highlight the important role of the mTOR cascade in aneurysm progression and the potential application of rapamycin as a therapeutic candidate for AAA.
- abdominal aortic aneurysm
- smooth muscle cell
- Copyright © 2016, American Journal of Physiology-Heart and Circulatory Physiology