ESTADO DA ARTE DO MECANISMO AUTOFÁGICO COMO ESTRATÉGIA TERAPÊUTICA NA CARDIOLOGIA

Authors

  • Ercília Ramalho Universidade Anhanguera de São Paulo (UNIAN-SP)
  • Vânia Olivon Universidade Anhanguera de São Paulo (UNIAN-SP)
  • Waleska Kerllen Martins Universidade Anhanguera de São Paulo (UNIAN-SP)

Keywords:

Autofagia, Doença cardiovascular, Inibição/Ativação da Autofagia

Abstract

A autofagia desempenha um papel fundamental na manutenção da função cardíaca e da homeostase vascular, além de se destacar também na patogênese de diversas doenças cardiovasculares (DCV). No entanto, a dinâmica do fluxo de autofagia parece diferir em cada um dos tipos de DCV, cuja patogênese pode estar intrinsecamente associada a sinais autofágicos distintos (efeito protetor ou patogênico). Aqui, discutimos abordagens de sucesso voltadas à regulação da iniciação da autofagia para abordar a terapia direcionada às doenças cardiovasculares.

Author Biography

  • Waleska Kerllen Martins, Universidade Anhanguera de São Paulo (UNIAN-SP)

    Laboratório de Célula e Membrana, UNIAN-SP (2017 - atual)

    Universidade Santo Amaro (2015 - 2017)

    Universidade de São Paulo (2009 - 2015)

    FUNED (2007 - 2009)

    Hospital A. C. Camargo (2003 - 2007)

    Ludwig Institute for Cancer Research (1999 - 2003)

References

Yang Y, Klionsky DJ. Autophagy and disease : unanswered questions. Cell Death Differ. 2020;

Nishida K, Otsu K. Autophagy during cardiac remodeling. J Mol Cell Cardiol. 2016;95:11–8.

Xu L, Brink M. mTOR, cardiomyocytes and inflammation in cardiac hypertrophy. Biochim Biophys Acta - Mol Cell Res. 2016;1863(7):1894–903.

Bravo-San Pedro JM, Kroemer G, Galluzzi L. Autophagy and Mitophagy in Cardiovascular Disease. Circ Res. 2017;120(11):1812–24.

Gatica D, Chiong M, Lavandero S, Klionsky DJ. Molecular Mechanisms of Autophagy in the Cardiovascular System. Circ Res. 2015 Jan 30;116(3):456–67.

Doenças cardiovasculares - OPAS/OMS | Organização Pan-Americana da Saúde.

Knuuti J, Wijns W, Achenbach S, Agewall S, Barbato E, Bax JJ, et al. 2019 ESC guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J. 2020;41(3):407–77.

Rohde LEP, Montera MW, Bocchi EA, Clausell NO, de Albuquerque DC, Rassi S, et al. Diretriz brasileira de insuficiência cardíaca crônica e aguda. Arq Bras Cardiol. 2018;111(3):436–539.

Libby P. Mechanisms of acute coronary syndromes and their implications for therapy. N Engl J Med. 2013;368(21):2004–13.

Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation. 2002 Mar;105(9):1135–43.

Avezedo S, Victor EG, Oliveira DC de. Diabetes mellitus e aterosclerose: noções básicas da fisiopatologia para o clínico geral: [revisão]. Rev Soc Bras Clín Méd. 2010;

Hansson GK. Inflammation, Atherosclerosis, and Coronary Artery Disease. Vol. 352, n engl j med. 2005.

Kim J, Kundu M, Viollet B, Guan K-L. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol. 2011 Feb 23;13(2):132–41.

Di Malta C, Cinque L, Settembre C. Transcriptional Regulation of Autophagy: Mechanisms and Diseases. Front Cell Dev Biol. 2019;7(July):1–10.

Jean S, Kiger AA. Classes of phosphoinositide 3-kinases at a glance. J Cell Sci. 2014;127(5):923–8.

Ohashi Y, Tremel S, Williams RL. VPS34 complexes from a structural perspective. J Lipid Res. 2019;60(2):229–41.

Yu L, Chen Y, Tooze SA. Autophagy pathway: Cellular and molecular mechanisms. Autophagy. 2018;14(2):207–15.

Zachari M, Ganley IG. The mammalian ULK1 complex and autophagy initiation. Essays Biochem. 2017 Dec 12;61(6):585–96.

Grasso D, Renna FJ, Vaccaro MI. Initial steps in Mammalian autophagosome biogenesis. Front Cell Dev Biol. 2018;6(OCT):1–10.

Itakura E, Mizushima N. Characterization of autophagosome formation site by a hierarchical analysis of mammalian Atg proteins. Autophagy. 2010 Aug 16;6(6):764–76.

Axe EL, Walker SA, Manifava M, Chandra P, Roderick HL, Habermann A, et al. Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum. J Cell Biol. 2008 Aug 25;182(4):685–701.

Orsi A, Razi M, Dooley HC, Robinson D, Weston AE, Collinson LM, et al. Dynamic and transient interactions of Atg9 with autophagosomes, but not membrane integration, are required for autophagy. Klumperman J, editor. Mol Biol Cell. 2012 May 15;23(10):1860–73.

Karanasios E, Walker SA, Okkenhaug H, Manifava M, Hummel E, Zimmermann H, et al. Autophagy initiation by ULK complex assembly vesicles. Nat Commun. 2016;7:1–17.

Shpilka T, Mizushima N, Elazar Z. Ubiquitin-like proteins and autophagy at a glance. J Cell Sci. 2012;125(10):2343–8.

Mohan J, Wollert T. Human ubiquitin-like proteins as central coordinators in autophagy. Interface Focus. 2018;8(5).

Galluzzi L, Baehrecke EH, Ballabio A, Boya P, Bravo?San Pedro JM, Cecconi F, et al. Molecular definitions of autophagy and related processes. EMBO J. 2017;36(13):1811–36.

North BJ, Sinclair DA. The Intersection Between Aging and Cardiovascular Disease. Circ Res. 2012 Apr 13;110(8):1097–108.

Shioi T, McMullen JR, Tarnavski O, Converso K, Sherwood MC, Manning WJ, et al. Rapamycin attenuates load-induced cardiac hypertrophy in mice. Circulation. 2003;107(12):1664–70.

McMullen JR, Sherwood MC, Tarnavski O, Zhang L, Dorfman AL, Shioi T, et al. Inhibition of mTOR signaling with rapamycin regresses established cardiac hypertrophy induced by pressure overload. Circulation. 2004;109(24):3050–5.

Martinet W, Verheye S, De Meyer GRY. Selective depletion of macrophages in atherosclerotic plaques via macrophage-specific initiation of cell death. Trends Cardiovasc Med. 2007 Feb;17(2):69–75.

Sousa JE, Serruys PW, Costa MA. New frontiers in cardiology: Drug-eluting stents: Part I. Circulation. 2003;107(17):2274–9.

Verheye S, Martinet W, Kockx MM, Knaapen MWM, Salu K, Timmermans JP, et al. Selective Clearance of Macrophages in Atherosclerotic Plaques by Autophagy. J Am Coll Cardiol. 2007;49(6):706–15.

Martinet W, De Loof H, De Meyer GRY. mTOR inhibition: a promising strategy for stabilization of atherosclerotic plaques. Atherosclerosis. 2014 Apr;233(2):601–7.

Buss SJ, Riffel JH, Katus HA, Hardt SE. Augmentation of autophagy by mTOR-inhibition in myocardial infarction: When size matters. Autophagy. 2010;6(2):304–6.

Cho YS, Yen CN, Shim JS, Kang DH, Kang SW, Liu JO, et al. Antidepressant indatraline induces autophagy and inhibits restenosis via suppression of mTOR/S6 kinase signaling pathway. Sci Rep. 2016;6(September):1–9.

Kim Y, Park JK, Seo JH, Ryu HS, Lim KS, Jeong MH, et al. A rapamycin derivative, biolimus, preferentially activates autophagy in vascular smooth muscle cells. Sci Rep. 2018;8(1):1–13.

Mu F, Jiang Y, Ao F, Wu H, You Q, Chen Z. RapaLink-1 plays an antithrombotic role in antiphospholipid syndrome by improving autophagy both in vivo and vitro. Biochem Biophys Res Commun. 2020 Apr;525(2):384–91.

Chang K, Kang P, Liu Y, Huang K, Miao T, Sagona AP, et al. TGFB-INHB/activin signaling regulates age-dependent autophagy and cardiac health through inhibition of MTORC2. Autophagy. 2020 Oct 2;16(10):1807–22.

Akhurst RJ, Hata A. Targeting the TGF? signalling pathway in disease. Nat Rev Drug Discov. 2012 Oct 24;11(10):790–811.

Kanamori H, Naruse G, Yoshida A, Minatoguchi S, Watanabe T, Kawaguchi T, et al. Metformin Enhances Autophagy and Provides Cardioprotection in ?-Sarcoglycan Deficiency-Induced Dilated Cardiomyopathy. Circ Hear Fail. 2019;12(4):1–13.

Xie Z, He C, Zou MH. AMP-activated protein kinase modulates cardiac autophagy in diabetic cardiomyopathy. Autophagy. 2011;7(10):1254–5.

Shimizu I, Minamino T. Physiological and pathological cardiac hypertrophy. J Mol Cell Cardiol. 2016;97:245–62.

McMullen JR, Shioi T, Huang WY, Zhang L, Tarnavski O, Bisping E, et al. The Insulin-like Growth Factor 1 Receptor Induces Physiological Heart Growth via the Phosphoinositide 3-Kinase(p110?) Pathway. J Biol Chem. 2004;279(6):4782–93.

Sciarretta S, Zhai P, Shao D, Maejima Y, Robbins J, Volpe M, et al. Rheb is a Critical Regulator of Autophagy During Myocardial Ischemia. Circulation. 2012 Mar 6;125(9):1134–46.

Eisenberg T, Abdellatif M, Schroeder S, Primessnig U, Stekovic S, Pendl T, et al. Cardioprotection and lifespan extension by the natural polyamine spermidine. Nat Med. 2016;22(12):1428–38.

Yan J, Yan J, Wang Y, Ling Y, Song X, Wang S, et al. Spermidine?enhanced autophagic flux improves cardiac dysfunction following myocardial infarction by targeting the AMPK/mTOR signalling pathway. Br J Pharmacol. 2019 Jul 17;bph.14706.

Li RL, Wu SS, Wu Y, Wang XX, Chen HY, Xin J juan, et al. Irisin alleviates pressure overload-induced cardiac hypertrophy by inducing protective autophagy via mTOR-independent activation of the AMPK-ULK1 pathway. J Mol Cell Cardiol. 2018;121(July):242–55.

Li R, Wang X, Wu S, Wu Y, Chen H, Xin J, et al. Irisin ameliorates angiotensin II-induced cardiomyocyte apoptosis through autophagy. J Cell Physiol. 2019;234(10):17578–88.

Sun GZ, Meng FJ, Cai HQ, Diao XB, Zhang B, Bai XP. Ginsenoside Rg3 protects heart against isoproterenol-induced myocardial infarction by activating AMPK mediated autophagy. Cardiovasc Diagn Ther. 2020;10(2):153–60.

Chen WR, Yang JQ, Liu F, Shen XQ, Zhou YJ. Melatonin attenuates vascular calcification by activating autophagy via an AMPK/mTOR/ULK1 signaling pathway. Exp Cell Res. 2020;389(1):111883.

Yamaguchi O. Autophagy in the heart. Circ J. 2019;83(4):697–704.

Huang C, Liu W, Perry CN, Yitzhaki S, Lee Y, Yuan H, et al. Autophagy and protein kinase C are required for cardioprotection by sulfaphenazole. Am J Physiol Heart Circ Physiol. 2010;298(2):H570–9.

Sala-Mercado JA, Wider J, Reddy Undyala VV, Jahania S, Yoo W, Mentzer RM, et al. Profound cardioprotection with chloramphenicol succinate in the swine model of myocardial ischemia-reperfusion injury. Circulation. 2010;122(11 SUPPL. 1):179–85.

Giricz Z, Varga Z V., Koncsos G, Nagy CT, Görbe A, Mentzer RM, et al. Autophagosome formation is required for cardioprotection by chloramphenicol. Life Sci. 2017 Oct;186(1):11–6.

Sciarretta S, Yee D, Nagarajan N, Bianchi F, Saito T, Valenti V, et al. Trehalose-Induced Activation of Autophagy Improves Cardiac Remodeling After Myocardial Infarction. J Am Coll Cardiol. 2018 May;71(18):1999–2010.

Evans TD, Jeong SJ, Zhang X, Sergin I, Razani B. TFEB and trehalose drive the macrophage autophagy-lysosome system to protect against atherosclerosis. Autophagy. 2018;14(4):724–6.

Alexanian I, Parissis J, Farmakis D, Pantziou C, Ikonomidis I, Paraskevaidis I, et al. Selenium contributes to myocardial injury and cardiac remodeling in heart failure. Int J Cardiol. 2014 Sep;176(1):272–3.

Chen J. An original discovery: Selenium deficiency and Keshan disease (an endemic heart disease). Asia Pac J Clin Nutr. 2012;21(3):320–6.

Steinbrenner H, Speckmann B, Klotz LO. Selenoproteins: Antioxidant selenoenzymes and beyond. Arch Biochem Biophys. 2016;595:113–9.

Liu ZW, Zhu HT, Chen KL, Qiu C, Tang KF, Niu XL. Selenium attenuates high glucose-induced ROS/TLR-4 involved apoptosis of rat cardiomyocyte. Biol Trace Elem Res. 2013;156(1–3):262–70.

Chen X, Xu J, Liu D, Sun Y, Qian G, Xu S, et al. The aggravating effect of selenium deficiency on T-2 toxin-induced damage on primary cardiomyocyte results from a reduction of protective autophagy. Chem Biol Interact. 2019;300(November 2018):27–34.

He J, Zhang G, Pang Q, Yu C, Xiong J, Zhu J, et al. SIRT6 reduces macrophage foam cell formation by inducing autophagy and cholesterol efflux under ox-LDL condition. FEBS J. 2017;284(9):1324–37.

Gu HF, Li HZ, Tang YL, Tang XQ, Zheng XL, Liao DF. Nicotinate-curcumin impedes foam cell formation from THP-1 cells through restoring autophagy flux. PLoS One. 2016;11(4):1–15.

Zhang L, Liu Q, Zhang H, Wang XD, Chen SY, Yang Y, et al. C1q/TNF-Related Protein 9 Inhibits THP-1 Macrophage Foam Cell Formation by Enhancing Autophagy. J Cardiovasc Pharmacol. 2018;72(4):167–75.

Cao DJ, Wang Z V, Battiprolu PK, Jiang N, Morales CR, Kong Y, et al. Histone deacetylase (HDAC) inhibitors attenuate cardiac hypertrophy by suppressing autophagy. Proc Natl Acad Sci U S A. 2011;108(10):4123–8.

Wang Y, Chen P, Wang L, Zhao J, Zhong Z, Wang Y, et al. Inhibition of Histone Deacetylases Prevents Cardiac Remodeling after Myocardial Infarction by Restoring Autophagosome Processing in Cardiac Fibroblasts. Cell Physiol Biochem. 2018;49(5):1999–2011.

Shen Q, Shi Y, Liu J, Su H, Huang J, Zhang Y, et al. Acetylation of STX17 (syntaxin 17) controls autophagosome maturation. Autophagy. 2020 Apr 15;0(0):1–13.

Ba L, Gao J, Chen Y, Qi H, Dong C, Pan H, et al. Allicin attenuates pathological cardiac hypertrophy by inhibiting autophagy via activation of PI3K/Akt/mTOR and MAPK/ERK/mTOR signaling pathways. Phytomedicine. 2019;58(November 2017):1–10.

Sharma M, Kambadur R, Matthews KG, Somers WG, Devlin GP, Conaglen J V., et al. Myostatin, a transforming growth factor-? superfamily member, is expressed in heart muscle and is upregulated in cardiomyocytes after infarct. J Cell Physiol. 1999;180(1):1–9.

Zhang C, McFarlane C, Lokireddy S, Bonala S, Ge X, Masuda S, et al. Myostatin-deficient mice exhibit reduced insulin resistance through activating the AMP-activated protein kinase signalling pathway. Diabetologia. 2011;54(6):1491–501.

Qi H, Ren J, Ba L, Song C, Zhang Q, Cao Y, et al. MSTN Attenuates Cardiac Hypertrophy through Inhibition of Excessive Cardiac Autophagy by Blocking AMPK /mTOR and miR-128/PPAR?/NF-?B. Mol Ther - Nucleic Acids. 2020;19(March):507–22.

Ebner N, Sliziuk V, Scherbakov N, Sandek A. Muscle wasting in ageing and chronic illness. ESC Hear Fail. 2015;2(2):58–68.

Noh HS, Shin IW, Ha JH, Hah Y-S, Baek SM, Kim DR. Propofol protects the autophagic cell death induced by the ischemia/reperfusion injury in rats. Mol Cells. 2010 Nov;30(5):455–60.

Cui DR, Wang L, Jiang W, Qi AH, Zhou QH, Zhang XL. Propofol prevents cerebral ischemia-triggered autophagy activation and cell death in the rat hippocampus through the NF-?B/p53 signaling pathway. Neuroscience. 2013 Aug 29;246:117–32.

Wang Y, Zhang K, Qi X, Yang G, Wang H, Zhang Z, et al. Effects of propofol on LC3II and mTOR/p?mTOR expression during ischemia?reperfusion myocardium injury in rats with type 2 diabetes mellitus. Exp Ther Med. 2020 Feb 7;2441–8.

Chen WR, Liu H Bin, Chen YD, Sha Y, Ma Q, Zhu PJ, et al. Melatonin attenuates myocardial ischemia/reperfusion injury by inhibiting autophagy via an AMPK/mTOR Signaling Pathway. Cell Physiol Biochem. 2018;47(5):2067–76.

Huang Z, Han Z, Ye B, Dai Z, Shan P, Lu Z, et al. Berberine alleviates cardiac ischemia/reperfusion injury by inhibiting excessive autophagy in cardiomyocytes. Eur J Pharmacol. 2015;762:1–10.

Wu S, Chang G, Gao L, Jiang D, Wang L, Li G, et al. Trimetazidine protects against myocardial ischemia/reperfusion injury by inhibiting excessive autophagy. J Mol Med. 2018;96(8):791–806.

Li X, Hu X, Wang JiH, Xu W, Yi C, Ma R, et al. Inhibition of autophagy via activation of PI3K/Akt/mTOR pathway contributes to the protection of hesperidin against myocardial ischemia/reperfusion injury. Int J Mol Med. 2018;42(4):1917–24.

Published

2022-07-15

Issue

Section

Artigo de revisão

How to Cite

ESTADO DA ARTE DO MECANISMO AUTOFÁGICO COMO ESTRATÉGIA TERAPÊUTICA NA CARDIOLOGIA. (2022). Arquivos Catarinenses De Medicina, 50(4). https://revista.acm.org.br/arquivos/article/view/1003

Similar Articles

1-10 of 472

You may also start an advanced similarity search for this article.

Most read articles by the same author(s)