Everolimus-induced mTOR inhibition selectively depletes macrophages in atherosclerotic plaques by autophagy

Autophagy

Volumn 3, Issue 3, 2007, Pages 241-244

  Martinet, Wim ^a   Verheye, Stefan ^b   De Meyer, Guido R Y ^a  

^a UNIVERSITY OF ANTWERP   (Belgium)

^b MIDDELHEIM HOSPITAL   (Belgium)

Author keywords

Atherosclerosis; Autophagy; Everolimus; Macrophage; mTOR; Smooth muscle cell

Indexed keywords

CELL PROTEIN; EVEROLIMUS; LC3 PROTEIN; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; ATHEROSCLEROTIC PLAQUE; AUTOPHAGY; BLOOD VESSEL WALL; CELL DEATH; CELL TYPE; CELL VACUOLE; CHOLESTEROL INTAKE; CONTROLLED STUDY; CYTOPLASM; DRUG ELUTING STENT; ENZYME INHIBITION; LIGHT CHAIN; MACROPHAGE; MICROTUBULE; NONHUMAN; PROTEIN DEGRADATION; RABBIT; SMOOTH MUSCLE FIBER;

MAMMALIA; ORYCTOLAGUS CUNICULUS;

EID: 34248561123     PISSN: 15548627     EISSN: 15548635     Source Type: Journal    
DOI: 10.4161/auto.3711     Document Type: Article

References (25)

1. Thomas G, Hall MN. TOR signalling and control of cell growth. Curr Opin Cell Biol 1997; 9:782-7.
2. Dennis PB, Fumagalli S, Thomas G. Target of rapamycin (TOR): Balancing the opposing forces of protein synthesis and degradation. Curr Opin Genet Dev 1999; 9:49-54.
3. Easton JB, Houghton PJ. Therapeutic potential of target of rapamycin inhibitors. Expert Opin Ther targets 2004; 8:551-64.
4. Easton JB, Houghton PJ. mTOR and cancer therapy. Oncogene 2006; 25:6436-46.
5. Noda T, Ohsumi Y. Tor, a phosphatidylinositol kinase homologue, controls autophagy in yeast. J Biol Chem 1998; 273:3963-6.
6. Ravikumar B, Vachet C, Berger Z, Davies JE, Luo S, Oroz LG, Scaravilli F, Easton DF, Duden R, O'Kane CJ, Rubinsztein DC. Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat Genet 2004; 36:585-95.
7. Woltman AM, van der Kooij SW, Coffer PJ, Offringa R, Daha MR, van Kooten C. Rapamycin specifically interferes with GM-CSF signaling in human dendritic cells, leading to apoptosis via increased p27/KIP1 expression. Blood 2003; 101:1439-45.
8. Huang S, Shu L, Dilling MB, Easton J, Harwood FC, Ichijo H, Houghton PJ. Sustained activation of the JNK cascade and rapamyrin-induced apoptosis are suppressed by p53/p21(Cip1). Mol Cell 2003; 11:1491-501.
9. Verheye S, Martinet W, Kockx MM, Knaapen MWM, Salu K, Timmermans JP, Ellis JT, Kilpatrick DL, De Meyer GRY. Selective clearance of macrophages in atherosclerotic plaques by autophagy. J Am Coll Cardiol 2007, (In press).
10. Ross R. Atherosclerosis - An inflammatory disease. New Engl J Med 1999; 340:115-126.
11. Newby AC. Dual role of matrix metalloproteinases (matrixins) in intimal thickening and atherosclerotic plaque rupture. Physiol Rev 2005; 85:1-31.
12. Croons V, Martinet W, Herman AG, Timmermans JP, De Meyer GRY. Selective clearance of macrophages in atherosclerotic plaques by the protein synthesis inhibitor cycloheximide. J Pharmacol Exp Ther 2007, (In press).
13. De Meyer GRY, Kockx MM, Knaapen MWM, Martinet W, De Cleen DMM, Bult H, Herman AG. Nitric oxide donor molsidomine favors features of atherosclerotic plaque stability during cholesterol lowering in rabbits. J Cardiovasc Pharmacol 2003; 41:970-8.
14. Bjornheden T, Bondjers G. Oxygen consumption in aortic tissue from rabbits with diet-induced atherosclerosis. Arteriosclerosis 1987; 7:238-47.
15. Lutgens E, de Muinck ED, Kitslaar PJEHM, Tordoir JHM, Wellens HJJ, Daemen MJAP. Biphasic pattern of cell turnover characterizes the progression from fatty streaks to ruptured human atherosclerotic plaques. Cardiovasc Res 1999; 41:473-9.
16. Martinet W, Knaapen MWM, De Meyer GRY, Herman AG, Kockx MM. Elevated levels of oxidative DNA damage and DNA repair enzymes in human atherosclerotic plaques. Circulation 2002; 106:927-32.
17. Martin KA, Rzucidlo EM, Merenick BL, Fingar DC, Brown DJ, Wagner RJ, Powell RJ. The mTOR/p70 S6K1 pathway regulates vascular smooth muscle cell differentiation. Am J Physiol Cell Physiol 2004; 286:C507-17.
18. Pearson RB, Dennis PB, Han JW, Williamson NA, Kozma SC, Wettenhall RE, Thomas G. The principal target of rapamycin-induced p70s6k inactivation is a novel phosphorylation site within a conserved hydrophobic domain. EMBO J 1995; 14:5279-87.
19. Abeliovich H. Regulation of autophagy by the target of rapamycin (Tor) proteins. In: Klionsky DJ, ed. Autophagy. Georgetown: Landes Bioscience, 2004:60-69.
20. Kamada Y, Funakoshi T, Shintani T, Nagano K, Ohsumi M, Ohsumi Y. Tor-mediated induction of autophagy via an Apg1 protein kinase complex. J Cell Biol 2000; 150:1507-13.
21. Jiang Y, Broach JR. Tor proteins and protein phosphatase 2A reciprocally regulate Tap42 in controlling cell growth in yeast. EMBO J 1999; 18:2782-92.
22. Huang WP, Scott SV, Kim J, Klionsky DJ. The itinerary of a vesicle component, Aut7p/Cvt5p, terminates in the yeast vacuole via the autophagy/Cvt pathways. J Biol Chem 2000; 275:5845-51.
23. Chan TF, Bertram PG, Ai W, Zheng S. Regulation of APG14 expression by the GATA-type transcription factor Gln3p. J Biol Chem 2001; 276:6463-7.
24. Nanahoshi M, Tsujishita Y, Tokunaga C, Inui S, Sakaguchi N, Hara K, Yonezawa K. Alpha4 protein as a common regulator of type 2A-related serine/threonine protein phosphatases. FEBS Lett 1999; 446:108-12.
25. Tabas I. Consequences and therapeutic implications of macrophage apoptosis in atherosclerosis: The importance of lesion stage and phagocytic efficiency. Arterioscler Thromb Vasc Biol 2005; 25:2255-64.