title: Macrophage autophagy in atherosclerosis.
abstract: Macrophages play crucial roles in atherosclerotic immune responses. Recent investigation into macrophage autophagy (AP) in atherosclerosis has demonstrated a novel pathway through which these cells contribute to vascular inflammation. AP is a cellular catabolic process involving the delivery of cytoplasmic contents to the lysosomal machinery for ultimate degradation and recycling. Basal levels of macrophage AP play an essential role in atheroprotection during early atherosclerosis. However, AP becomes dysfunctional in the more advanced stages of the pathology and its deficiency promotes vascular inflammation, oxidative stress, and plaque necrosis. In this paper, we will discuss the role of macrophages and AP in atherosclerosis and the emerging evidence demonstrating the contribution of macrophage AP to vascular pathology. Finally, we will discuss how AP could be targeted for therapeutic utility.
authors: Department of Experimental Pharmacology, University of Naples Federico II, 80131 Naples, Italy.
authors: Maria Chiara
authors: MC
authors: Maiuri
authors: Gianluca
authors: G
authors: Grassia
authors: Andrew M
authors: AM
authors: Platt
authors: Rosa
authors: R
authors: Carnuccio
authors: Armando
authors: A
authors: Ialenti
authors: Pasquale
authors: P
authors: Maffia
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000503:physiopathology*; D001343:Autophagy / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000502:physiology*
references: J Cell Biol. 2009 Jul 27;186(2):255-68
references: 19635843
references: Arterioscler Thromb Vasc Biol. 2004 Aug;24(8):1359-66
references: 15178558
references: Nature. 2008 Nov 13;456(7219):264-8
references: 18849965
references: Arterioscler Thromb Vasc Biol. 2008 Feb;28(2):251-7
references: 18048768
references: Atherosclerosis. 2004 Jan;172(1):31-8
references: 14709354
references: Cancer Res. 2010 Jan 15;70(2):621-31
references: 20068177
references: Nature. 2007 Jun 28;447(7148):1121-5
references: 17589504
references: Nat Cell Biol. 2010 Sep;12(9):831-5
references: 20811355
references: Proc Natl Acad Sci U S A. 2008 Dec 9;105(49):19211-6
references: 19050071
references: Cell Metab. 2012 Jul 3;16(1):68-80
references: 22768840
references: J Biol Chem. 2003 Oct 24;278(43):41702-8
references: 12871942
references: Antioxid Redox Signal. 2011 Jun;14(11):2233-43
references: 20812858
references: Circulation. 2007 Mar 20;115(11):e326-8
references: 17372180
references: Nat Med. 2007 May;13(5):619-24
references: 17450150
references: Oncogene. 2008 Jun 5;27(25):3576-86
references: 18212742
references: Basic Res Cardiol. 2013 Jan;108(1):321
references: 23233268
references: Cell Host Microbe. 2009 Jun 18;5(6):527-49
references: 19527881
references: Immunol Rev. 2012 Sep;249(1):195-204
references: 22889223
references: J Cardiovasc Pharmacol. 2005 Oct;46(4):481-6
references: 16160601
references: Nat Immunol. 2006 Mar;7(3):311-7
references: 16462739
references: Sci Signal. 2010 May 25;3(123):ra42
references: 20501938
references: J Clin Invest. 2000 Apr;105(8):1095-108
references: 10772654
references: Eur J Cell Biol. 2007 Oct;86(10):605-16
references: 17643551
references: J Am Coll Cardiol. 2008 Apr 1;51(13):1258-65
references: 18371555
references: Methods Enzymol. 2009;452:181-97
references: 19200883
references: Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10340-10345
references: 16801531
references: Circulation. 2010 Aug 24;122(8):808-20
references: 20697023
references: Curr Opin Cell Biol. 2010 Apr;22(2):124-31
references: 20034776
references: Cell. 2006 Sep 8;126(5):955-68
references: 16959574
references: Nat Immunol. 2010 Feb;11(2):155-61
references: 20037584
references: Autophagy. 2007 Nov-Dec;3(6):620-2
references: 17786022
references: PLoS One. 2009 Sep 22;4(9):e7124
references: 19771169
references: Arterioscler Thromb Vasc Biol. 2008 Dec;28(12):2108-14
references: 18772495
references: Mol Cell. 2010 Oct 22;40(2):280-93
references: 20965422
references: Curr Biol. 2004 Dec 29;14(24):2217-27
references: 15620648
references: Arterioscler Thromb Vasc Biol. 2004 Dec;24(12):2296-301
references: 15458974
references: Proc Natl Acad Sci U S A. 1995 Aug 29;92(18):8264-8
references: 7667279
references: Curr Opin Cell Biol. 2010 Apr;22(2):252-62
references: 20116986
references: Atherosclerosis. 2008 May;198(1):39-48
references: 17980369
references: Cell. 2010 May 14;141(4):656-67
references: 20478256
references: Nat Cell Biol. 2009 Dec;11(12):1433-7
references: 19898463
references: J Immunol. 1986 Mar 1;136(5):1680-7
references: 3485132
references: Cell. 2008 Jan 11;132(1):27-42
references: 18191218
references: Autophagy. 2009 Jul;5(5):590-603
references: 19363298
references: Expert Opin Ther Pat. 2012 Sep;22(9):1053-79
references: 22860892
references: Autophagy. 2012 Nov;8(11):1690-2
references: 22874554
references: Circulation. 2008 Apr 1;117(13):1649-57
references: 18347211
references: Mol Cell. 2008 Apr 25;30(2):214-26
references: 18439900
references: Nat Immunol. 2011 Mar;12(3):222-30
references: 21151103
references: Cell. 1982 Jan;28(1):71-81
references: 6978185
references: Circ Res. 2008 Sep 12;103(6):571-2
references: 18796643
references: J Cell Biol. 2005 Sep 26;170(7):1101-11
references: 16186256
references: Nat Cell Biol. 2008 Jun;10(6):637-9
references: 18521069
references: PLoS One. 2010 Jul 23;5(7):e11765
references: 20668705
references: J Cell Biol. 2008 Aug 25;182(4):685-701
references: 18725538
references: Antioxid Redox Signal. 2006 Jan-Feb;8(1-2):152-62
references: 16487049
references: Science. 2012 Apr 6;336(6077):86-90
references: 22442384
references: Curr Opin Immunol. 2012 Feb;24(1):21-31
references: 22118953
references: J Mol Cell Cardiol. 2006 Aug;41(2):256-64
references: 16769083
references: Science. 2007 Mar 9;315(5817):1398-401
references: 17272685
references: Annu Rev Immunol. 2009;27:165-97
references: 19302038
references: Cell Microbiol. 2002 Jan;4(1):1-10
references: 11856168
references: Autophagy. 2011 Jun;7(6):657-9
references: 21490416
references: Proc Natl Acad Sci U S A. 2011 Oct 18;108(42):17396-401
references: 21969579
references: J Clin Invest. 2012 Sep;122(9):3114-26
references: 22886300
references: Cell Metab. 2012 Apr 4;15(4):534-44
references: 22440612
references: PLoS Biol. 2009 Feb 10;7(2):e38
references: 19209957
references: Am J Pathol. 1990 Jan;136(1):71-80
references: 2297051
references: Dev Cell. 2004 Apr;6(4):463-77
references: 15068787
references: Int J Cell Biol. 2012;2012:282041
references: 22536247
references: Pharmacol Ther. 2013 Feb;137(2):172-82
references: 23059425
references: Autophagy. 2011 May;7(5):541-3
references: 21412049
references: Cell Death Differ. 2005 Nov;12 Suppl 2:1542-52
references: 16247502
references: Science. 2006 Sep 8;313(5792):1438-41
references: 16888103
references: Immunity. 2003 Jul;19(1):71-82
references: 12871640
references: Genes Dev. 2004 Aug 15;18(16):1926-45
references: 15314020
references: EMBO J. 2007 May 16;26(10):2527-39
references: 17446862
references: PLoS One. 2011;6(9):e25436
references: 21980456
references: J Clin Invest. 2007 Jan;117(1):195-205
references: 17200719
references: Cell. 2009 Jun 12;137(6):1001-4
references: 19524504
references: Basic Res Cardiol. 2012 May;107(3):269
references: 22543675
references: Nat Cell Biol. 2010 Aug;12(8):747-57
references: 20639872
references: Circ Res. 2007 Mar 30;100(6):751-3
references: 17395878
references: J Am Coll Cardiol. 2007 Feb 13;49(6):706-15
references: 17291937
references: Curr Opin Cell Biol. 2005 Dec;17(6):596-603
references: 16226444
references: Arterioscler Thromb Vasc Biol. 2005 Jun;25(6):1256-61
references: 15831805
references: Cancer Biol Ther. 2011 Jan 15;11(2):169-76
references: 21263212
references: Circ Res. 2009 Feb 13;104(3):304-17
references: 19213965
references: Nature. 2001 May 31;411(6837):599-603
references: 11385576
references: Nat Rev Mol Cell Biol. 2008 Dec;9(12):1004-10
references: 18971948
references: Cancer Res. 2010 Jan 1;70(1):288-98
references: 20028854
references: Mech Ageing Dev. 2002 Apr 30;123(8):1121-31
references: 12044962
references: J Clin Invest. 1999 Jun;103(11):1547-60
references: 10359564
references: Science. 2005 Feb 4;307(5710):727-31
references: 15576571
references: Nature. 2007 Dec 20;450(7173):1253-7
references: 18097414
references: Arthritis Rheum. 2006 Mar;54(3):927-38
references: 16508977
references: Nature. 2009 Apr 30;458(7242):1131-5
references: 19339967
references: Science. 2010 Nov 5;330(6005):841-5
references: 20966214
references: Hum Mol Genet. 2006 Feb 1;15(3):433-42
references: 16368705
references: Curr Top Microbiol Immunol. 2009;335:33-70
references: 19802559
references: Nat Rev Drug Discov. 2009 Jan;8(1):33-40
references: 19116625
references: Cell. 2004 Dec 17;119(6):753-66
references: 15607973
references: Circ Res. 1998 Aug 24;83(4):378-87
references: 9721694
references: Exp Cell Res. 2012 Jul 1;318(11):1187-92
references: 22245582
references: J Physiol. 2012 Jul 15;590(14):3305-16
references: 22570377
references: Exp Cell Res. 2011 Jun 10;317(10):1437-53
references: 21420401
references: Basic Res Cardiol. 2011 Sep;106(5):749-60
references: 21611880
references: EMBO J. 2010 Oct 6;29(19):3421-33
references: 20808283
references: Curr Opin Lipidol. 2009 Oct;20(5):370-8
references: 19741337
references: Trends Immunol. 2011 Oct;32(10):470-7
references: 21664185
references: Br J Pharmacol. 2008 Jul;154(6):1236-46
references: 18469840
references: Nature. 2010 Apr 29;464(7293):1357-61
references: 20428172
references: Nat Genet. 2004 Jun;36(6):585-95
references: 15146184
references: Cell Host Microbe. 2008 Nov 13;4(5):458-69
references: 18996346
references: Am J Pathol. 1981 May;103(2):181-90
references: 7234961
references: Nat Rev Mol Cell Biol. 2007 Sep;8(9):741-52
references: 17717517
references: J Biol Chem. 2011 May 27;286(21):18890-902
references: 21454634
references: Int J Pharm. 2012 Jan 17;422(1-2):495-503
references: 22119964
references: J Exp Med. 2006 May 15;203(5):1273-82
references: 16682495
references: Cell Death Differ. 2007 Jun;14(6):1117-28
references: 17363964
references: Nat Cell Biol. 2006 Jul;8(7):688-99
references: 16799551
references: Cell. 2011 Apr 29;145(3):341-55
references: 21529710
references: Immunity. 2007 Sep;27(3):505-17
references: 17892853
references: Nat Chem Biol. 2007 Jun;3(6):331-8
references: 17486044
references: EMBO J. 2008 Apr 9;27(7):1110-21
references: 18337753
references: Science. 2005 Jan 28;307(5709):593-6
references: 15591165
references: Nat Cell Biol. 2008 Jun;10(6):676-87
references: 18454141
references: Nat Cell Biol. 2002 Sep;4(9):648-57
references: 12172553
references: Arterioscler Thromb Vasc Biol. 2008 Aug;28(8):1421-8
references: 18451332
references: Cell Metab. 2012 Apr 4;15(4):545-53
references: 22445600
references: Immunol Rev. 2007 Oct;219:187-203
references: 17850490
references: J Leukoc Biol. 2012 Feb;91(2):229-43
references: 22131344
references: Toxicol Appl Pharmacol. 2012 Aug 1;262(3):265-72
references: 22627060
references: Immunol Cell Biol. 2006 Oct;84(5):448-54
references: 16942488
references: Proc Natl Acad Sci U S A. 2005 Jun 7;102(23):8204-9
references: 15928081
references: Am J Physiol Endocrinol Metab. 2010 Apr;298(4):E751-60
references: 20103737
references: EMBO J. 2011 Nov 11;30(24):4908-20
references: 22081109
references: Cancer Res. 2006 Feb 1;66(3):1500-8
references: 16452206
references: Int J Mol Med. 2012 Apr;29(4):613-8
references: 22293957
references: Nat Cell Biol. 2009 Apr;11(4):468-76
references: 19270693
references: Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2770-5
references: 19196953
references: Curr Opin Immunol. 2006 Feb;18(1):49-53
references: 16338128
references: J Biol Chem. 2007 Feb 23;282(8):5641-52
references: 17182613
references: J Exp Med. 2011 Dec 19;208(13):2625-32
references: 22162830
references: Cancer Res. 2007 Jul 15;67(14):6745-52
references: 17638885
references: Cancer Res. 2007 Nov 15;67(22):10804-12
references: 18006825
references: Cell Death Differ. 2013 Jan;20(1):3-11
references: 22595754
references: J Biol Chem. 2000 Sep 8;275(36):27823-31
references: 10880512
references: Trends Cardiovasc Med. 2008 Aug;18(6):228-32
references: 19185814
references: Nature. 2011 May 19;473(7347):317-25
references: 21593864
references: Mol Biol Cell. 2008 Dec;19(12):5360-72
references: 18843052
references: Immunol Rev. 2011 Mar;240(1):92-104
references: 21349088
references: Immunity. 2007 Jul;27(1):135-44
references: 17658277
references: Immunity. 2007 Jul;27(1):11-21
references: 17663981
references: Oncogene. 2008 Dec;27 Suppl 1:S137-48
references: 19641499
references: J Cell Biol. 2010 Sep 6;190(5):881-92
references: 20819940
references: Blood. 2012 May 10;119(19):4527-31
references: 22452982
references: Br J Pharmacol. 2009 Mar;156(5):774-85
references: 19220291
references: Nature. 2011 Jan 20;469(7330):323-35
references: 21248839
references: J Clin Invest. 2007 Jan;117(1):185-94
references: 17200718
references: Nat Cell Biol. 2007 Oct;9(10):1102-9
references: 17909521
references: Arterioscler Thromb Vasc Biol. 2011 Dec;31(12):2787-91
references: 22096098
references: J Cell Biol. 2010 Jun 14;189(6):925-35
references: 20548099
references: J Cell Physiol. 2012 Jan;227(1):127-35
references: 21374592
references: Cell Metab. 2011 Jun 8;13(6):655-67
references: 21641547
references: Arterioscler Thromb Vasc Biol. 2012 Nov;32(11):2569-79
references: 22936340
references: Nat Cell Biol. 2007 Oct;9(10):1142-51
references: 17891140
references: Immunity. 2010 Mar 26;32(3):329-41
references: 20206555
references: Trends Biochem Sci. 2011 Jan;36(1):30-8
references: 20728362
references: Basic Res Cardiol. 2012 Nov;107(6):297
references: 22968334
references: EMBO J. 2010 Feb 3;29(3):619-31
references: 19959994
references: J Clin Invest. 2011 May;121(5):2025-36
references: 21505265
references: Nat Immunol. 2010 Jan;11(1):55-62
references: 19898471
references: Science. 2004 Nov 5;306(5698):1037-40
references: 15528445
references: Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):3030-4
references: 1557408
references: Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1238-43
references: 12552108
references: J Immunol. 2011 Oct 15;187(8):3953-61
references: 21911604
references: Proc Am Thorac Soc. 2010 Feb;7(1):40-7
references: 20160147
references: Cardiovasc Res. 2008 Aug 1;79(3):360-76
references: 18487233
references: Blood. 2010 Jan 21;115(3):e10-9
references: 19965649
references: Proc Natl Acad Sci U S A. 2010 Jun 8;107(23):10502-7
references: 20498061
references: Nat Rev Immunol. 2007 Oct;7(10):767-77
references: 17767194
references: Cell. 2006 Jul 14;126(1):121-34
references: 16839881
references: Autophagy. 2010 Feb;6(2):239-47
references: 20104019
references: Nature. 1997 Mar 20;386(6622):292-6
references: 9069289
references: Science. 2007 Aug 3;317(5838):666-70
references: 17673663
references: Cell Host Microbe. 2009 Sep 17;6(3):231-43
references: 19748465
references: Nat Cell Biol. 2009 Apr;11(4):385-96
references: 19270696
references: Am J Pathol. 2001 Aug;159(2):417-23
references: 11485899
references: Nat Chem Biol. 2011 Jan;7(1):9-17
references: 21164513
references: Nature. 2011 Jan 13;469(7329):221-5
references: 21124315
references: J Clin Invest. 2001 Sep;108(6):785-91
references: 11560944
references: J Immunol. 2011 Feb 1;186(3):1646-55
references: 21209283
references: Arterioscler Thromb Vasc Biol. 2009 Oct;29(10):1412-8
references: 19759373
references: Nature. 2002 May 16;417(6886):292-5
references: 12015604
references: J Biol Chem. 2009 Mar 20;284(12):8023-32
references: 19150980
references: Nat Immunol. 2009 May;10(5):461-70
references: 19381141
references: Cell. 2007 Mar 9;128(5):931-46
references: 17350577
references: Circulation. 2012 Apr 3;125(13):1673-83
references: 22388324
references: Mol Aspects Med. 2006 Oct-Dec;27(5-6):520-7
references: 16973207
references: Nat Rev Drug Discov. 2010 Feb;9(2):141-53
references: 20118962