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Everolimus-Induced mTOR Inhibition Selectively Depletes Macrophages in Atherosclerotic Plaques by Autophagy
| Content Provider | Scilit |
|---|---|
| Author | Martinet, Wim Verheye, Stefan Meyer, Guido R. Y. De |
| Copyright Year | 2007 |
| Description | Current pharmacological approaches to stabilize non-obstructive rupture-prone atherosclerotic plaques have only partially reduced the incidence of acute coronary syndromes and sudden death. Macrophages in these vulnerable plaques play a pivotal role in plaque destabilization, whereas smooth muscle cells promote plaque stability. In a recent study, we report that implantation of stents eluting everolimus, a mammalian target of rapamycin (mTOR) inhibitor, in atherosclerotic arteries of cholesterol-fed rabbits, led to a marked reduction in macrophage content without altering the amount of smooth muscle cells. Our in vitro studies showed that treatment of macrophages and smooth muscle cells with everolimus induced inhibition of translation of both cell types. However, cell death occurred only in macrophages and was characterized by bulk degradation of long-lived proteins, processing of microtubule associated protein light chain 3 (LC3), and cytoplasmic vacuolization, which are all markers of autophagy. Everolimus-induced autophagy was mediated by mTOR inhibition because cell viability was not affected using tacrolimus, an mTOR independent everolimus-analogue. These results provide proof-of-principle that macrophages in the vascular wall can be selectively cleared via induction of autophagy by mTOR inhibition. Therefore, stent-based delivery of an mTOR inhibitor may be a promising novel strategy for treatment of vulnerable atherosclerotic plaques. Addendum to: Selective Clearance of Macrophages in Atherosclerotic Plaques by Autophagy S. Verheye, W. Martinet, M.M. Kockx, M.W.M. Knaapen, K. Salu, J.-P. Timmermans, J.T. Ellis, D.L. Kilpatrick and G.R.Y. De Meyer J Am Coll Cardiol 2007; In Press |
| Related Links | https://www.tandfonline.com/doi/pdf/10.4161/auto.3711?needAccess=true |
| Ending Page | 244 |
| Page Count | 4 |
| Starting Page | 241 |
| ISSN | 15548627 |
| e-ISSN | 15548635 |
| DOI | 10.4161/auto.3711 |
| Journal | Autophagy |
| Issue Number | 3 |
| Volume Number | 3 |
| Language | English |
| Publisher | Informa UK Limited |
| Publisher Date | 2007-05-10 |
| Access Restriction | Open |
| Subject Keyword | Peripheral Vascular Disease Cell Death Everolimus Mtor Inhibition Vulnerable Macrophages in Atherosclerotic Plaques By Autophagy |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Molecular Biology |
