title: TRPV1 activation impedes foam cell formation by inducing autophagy in oxLDL-treated vascular smooth muscle cells.
abstract: Vascular smooth muscle cells (VSMCs) are an important origin of foam cells besides macrophages. The mechanisms underlying VSMC foam cell formation are relatively little known. Activation of transient receptor potential vanilloid subfamily 1 (TRPV1) and autophagy have a potential role in regulating foam cell formation. Our study demonstrated that autophagy protected against foam cell formation in oxidized low-density lipoprotein (oxLDL)-treated VSMCs; activation of TRPV1 by capsaicin rescued the autophagy impaired by oxLDL and activated autophagy-lysosome pathway in VSMCs; activation of TRPV1 by capsaicin impeded foam cell formation of VSMCs through autophagy induction; activation of TRPV1 by capsaicin induced autophagy through AMP-activated protein kinase (AMPK) signaling pathway. This study provides evidence that autophagy plays an important role in VSMC foam cell formation and highlights TRPV1 as a promising therapeutic target in atherosclerosis.
authors.affiliation: Department of Neurology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: B-H
authors.initials: BH
authors.lastname: Li
authors.affiliation: Department of Neurology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Y-W
authors.initials: YW
authors.lastname: Yin
authors.affiliation: Department of Neurology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Neurology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Pi
authors.affiliation: Department of Neurology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: L
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Neurology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: X-J
authors.initials: XJ
authors.lastname: Cao
authors.affiliation: Department of Neurology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: C-Y
authors.initials: CY
authors.lastname: Gao
authors.affiliation: Department of Neurology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: L-L
authors.initials: LL
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: J-C
authors.initials: JC
authors.lastname: Li
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D002211:Capsaicin / Q000494:pharmacology; D019610:Cytoprotection / Q000187:drug effects; D005487:Foam Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects*; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D050916:TRPV Cation Channels / Q000378:metabolism*
chemical_list: D008077:Lipoproteins, LDL; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; C099252:oxidized low density lipoprotein; D055372:AMP-Activated Protein Kinases; D002211:Capsaicin
references.citation: Cold Spring Harb Symp Quant Biol. 2011;76:155-64
references.pmid: 22071265
references.citation: Tissue Cell. 1987;19(5):657-63
references.pmid: 3321556
references.citation: Mol Pharmacol. 2009 Jun;75(6):1262-79
references.pmid: 19297520
references.citation: Dev Cell. 2004 Apr;6(4):463-77
references.pmid: 15068787
references.citation: Circ Res. 2007 Apr 13;100(7):1063-70
references.pmid: 17347480
references.citation: Cardiovasc Res. 2010 Apr 1;86(1):141-50
references.pmid: 20007688
references.citation: Circ Res. 2009 Feb 13;104(3):304-17
references.pmid: 19213965
references.citation: Cell Metab. 2010 Aug 4;12(2):130-41
references.pmid: 20674858
references.citation: Cell Metab. 2011 Jun 8;13(6):655-67
references.pmid: 21641547
references.citation: Cell Metab. 2005 Jul;2(1):9-19
references.pmid: 16054095
references.citation: Am J Physiol Cell Physiol. 2001 Mar;280(3):C709-18
references.pmid: 11171590
references.citation: Cell Metab. 2005 Jul;2(1):21-33
references.pmid: 16054096
references.citation: Dev Cell. 2008 Sep;15(3):344-357
references.pmid: 18804433
references.citation: Pflugers Arch. 2013 Sep;465(9):1303-16
references.pmid: 23605066
references.citation: Am J Physiol Endocrinol Metab. 2010 Jan;298(1):E1-7
references.pmid: 19887596
references.citation: Autophagy. 2008 Nov;4(8):1009-19
references.pmid: 18818525
references.citation: Int J Biochem Cell Biol. 2009 Mar;41(3):603-14
references.pmid: 18692155
references.citation: Pathol Res Pract. 1991 Mar;187(2-3):184-8
references.pmid: 2067998
references.citation: Cell. 2008 Jan 11;132(1):27-42
references.pmid: 18191218
references.citation: J Leukoc Biol. 2012 Sep;92(3):421-31
references.pmid: 22753949
references.citation: J Pathol. 2007 Jan;211(2):134-43
references.pmid: 17200947
references.citation: Circ Res. 2004 Feb 20;94(3):370-6
references.pmid: 14684629
references.citation: J Biol Chem. 2006 Nov 17;281(46):34870-9
references.pmid: 16990266
references.citation: Atherosclerosis. 2009 Jul;205(1):126-34
references.pmid: 19108833
references.citation: Curr Opin Cell Biol. 2010 Apr;22(2):132-9
references.pmid: 20056399
references.citation: Curr Opin Cell Biol. 2010 Apr;22(2):157-68
references.pmid: 20006481
references.citation: Mediators Inflamm. 2013;2013:925171
references.pmid: 23878415
references.citation: Nature. 2008 Feb 28;451(7182):1069-75
references.pmid: 18305538
references.citation: Cell Mol Life Sci. 1998 Jul;54(7):628-40
references.pmid: 9711230
references.citation: Cardiovasc Res. 2013 Mar 1;97(3):544-52
references.pmid: 23250921
references.citation: Cell Death Dis. 2013 Mar 14;4:e545
references.pmid: 23492776
references.citation: Nature. 2009 Apr 30;458(7242):1131-5
references.pmid: 19339967
references.citation: Curr Atheroscler Rep. 2008 Jun;10(3):216-23
references.pmid: 18489849
references.citation: Atherosclerosis. 2008 Nov;201(1):92-100
references.pmid: 18440006
references.citation: Nature. 1997 Oct 23;389(6653):816-24
references.pmid: 9349813
references.citation: Stroke. 2011 Nov;42(11):3245-51
references.pmid: 21852608
references.citation: News Physiol Sci. 2003 Dec;18:226-31
references.pmid: 14614154
references.citation: Proc Natl Acad Sci U S A. 2009 Nov 24;106(47):19860-5
references.pmid: 19910529
references.citation: Nat Genet. 2007 May;39(5):596-604
references.pmid: 17435756
references.citation: Atherosclerosis. 1991 Feb;86(2-3):227-37
references.pmid: 1872916
references.citation: Mol Cell. 2007 Jan 26;25(2):193-205
references.pmid: 17244528
references.citation: Int J Cardiol. 2013 Sep 30;168(2):1378-85
references.pmid: 23305858
references.citation: J Biol Chem. 2012 Apr 6;287(15):11761-8
references.pmid: 22354961
references.citation: Cardiovasc Res. 2011 Dec 1;92(3):504-13
references.pmid: 21908651
references.citation: Arteriosclerosis. 1984 Jul-Aug;4(4):323-40
references.pmid: 6466191
references.citation: Arteriosclerosis. 1990 Sep-Oct;10(5):680-7
references.pmid: 2403295
references.citation: Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3329-35
references.pmid: 14985505
references.citation: Cell Death Dis. 2013 Jun 13;4:e664
references.pmid: 23764845
references.citation: Biochem Biophys Res Commun. 2010 Dec 3;403(1):52-8
references.pmid: 21036148
references.citation: Br Heart J. 1993 Jan;69(1 Suppl):S30-7
references.pmid: 8427762
references.citation: Cell Death Dis. 2013 May 16;4:e638
references.pmid: 23681233
references.citation: J Biol Chem. 2005 Aug 12;280(32):29060-6
references.pmid: 15980064