Targeting the Autophagy-Lysosome Pathway in a Pathophysiologically Relevant Murine Model of Reversible Heart Failure

被引：10

作者：

Evans, Sarah ^{[1
]}

Ma, Xiucui ^{[1
]}

Wang, Xiqiang ^{[1
]}

Chen, Yana ^{[2
]}

Zhao, Chen ^{[1
]}

Weinheimer, Carla J. ^{[1
]}

Kovacs, Attila ^{[1
]}

Finck, Brian ^{[1
,2
]}

Diwan, Abhinav ^{[1
]}

Mann, Douglas L. ^{[1
]}

机构：

[1] Washington Univ, Sch Med, Ctr Cardiovasc Res, Cardiovasc Div, St Louis, MO USA

[2] Washington Univ, Sch Med, Div Geriatr & Nutr Sci, St Louis, MO USA

来源：

JACC-BASIC TO TRANSLATIONAL SCIENCE | 2022年 / 7卷 / 12期

基金：

美国国家卫生研究院;

关键词：

INSUFFICIENT AUTOPHAGY; DILATED CARDIOMYOPATHY; MYOCARDIAL RECOVERY; CARDIOMYOCYTES; CONTRIBUTES; ACTIVATION;

D O I：

10.1016/j.jacbts.2022.06.003

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The key biological "drivers" that are responsible for reverse left ventricle (LV) remodeling are not well understood. To gain an understanding of the role of the autophagy-lysosome pathway in reverse LV remodeling, we used a pathophysiologically relevant murine model of reversible heart failure, wherein pressure overload by transaortic constriction superimposed on acute coronary artery (myocardial infarction) ligation leads to a heart failure phenotype that is reversible by hemodynamic unloading. Here we show transaortic constriction thorn myocardial infarction leads to decreased flux through the autophagy-lysosome pathway with the accumulation of damaged proteins and organelles in cardiac myocytes, whereas hemodynamic unloading is associated with restoration of autophagic flux to normal levels with incomplete removal of damaged proteins and organelles in myocytes and reverse LV remodeling, suggesting that restoration of flux is insufficient to completely restore myocardial proteostasis. Enhancing autophagic flux with adeno-associated virus 9-transcription factor EB resulted in more favorable reverse LV remodeling in mice that had undergone hemodynamic unloading, whereas overexpressing transcription factor EB in mice that have not undergone hemodynamic unloading leads to increased mortality, suggesting that the therapeutic outcomes of enhancing autophagic flux will depend on the conditions in which flux is being studied. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

引用

页码：1214 / 1228

页数：15

共 53 条

[1] Insufficient autophagy in idiopathic pulmonary fibrosis [J].

Araya, Jun ;

Kojima, Jun ;

Takasaka, Naoki ;

Ito, Saburo ;

Fujii, Satoko ;

Hara, Hiromichi ;

Yanagisawa, Haruhiko ;

Kobayashi, Kenji ;

Tsurushige, Chikako ;

Kawaishi, Makoto ;

Kamiya, Noriki ;

Hirano, Jun ;

Odaka, Makoto ;

Morikawa, Toshiaki ;

Nishimura, Stephen L. ;

Kawabata, Yoshinori ;

Hano, Hiroshi ;

Nakayama, Katsutoshi ;

Kuwano, Kazuyoshi .

AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2013, 304 (01) :L56-L69

[2]

c&en. Cross R, 2019, AUT DRUGG YIN YANG C

[3] Myocardial Lipin 1 knockout in mice approximates cardiac effects of human LPIN1 mutations [J].

Chambers, Kari T. ;

Cooper, Michael A. ;

Swearingen, Alison R. ;

Brookheart, Rita T. ;

Schweitzer, George G. ;

Weinheimer, Carla J. ;

Kovacs, Attila ;

Koves, Timothy R. ;

Muoio, Deborah M. ;

McCommis, Kyle S. ;

Finck, Brian N. .

JCI INSIGHT, 2021, 6 (09)

[4] Angiotensin II Induces Skeletal Muscle Atrophy by Activating TFEB-Mediated MuRF1 Expression [J].

Du Bois, Philipp ;

Tortola, Cristina Pablo ;

Lodka, Doerte ;

Kny, Melanie ;

Schmidt, Franziska ;

Song, Kunhua ;

Schmidt, Sibylle ;

Bassel-Duby, Rhonda ;

Olson, Eric N. ;

Fielitz, Jens .

CIRCULATION RESEARCH, 2015, 117 (05) :424-436

[5] BETA-BLOCKER TREATMENT OF IDIOPATHIC AND ISCHEMIC DILATED CARDIOMYOPATHY IN PATIENTS WITH EJECTION FRACTIONS LESS-THAN-OR-EQUAL-TO-20-PERCENT [J].

ERLEBACHER, JA ;

BHARDWAJ, M ;

SURESH, A ;

LEBER, GB ;

GOLDWEIT, RS .

AMERICAN JOURNAL OF CARDIOLOGY, 1993, 71 (16) :1467-1469

[6] TNF receptor-activated factor 2 mediates cardiac protection through noncanonical NF-κB signaling [J].

Evans, Sarah ;

Tzeng, Huei-Ping ;

Veis, Deborah J. ;

Matkovich, Scot ;

Weinheimer, Carla ;

Kovacs, Attila ;

Barger, Philip M. ;

Mann, Douglas L. .

JCI INSIGHT, 2018, 3 (03)

[7] Insufficient autophagy promotes bronchial epithelial cell senescence in chronic obstructive pulmonary disease [J].

Fujii, Satoko ;

Hara, Hiromichi ;

Araya, Jun ;

Takasaka, Naoki ;

Kojima, Jun ;

Ito, Saburo ;

Minagawa, Shunsuke ;

Yumino, Yoko ;

Ishikawa, Takeo ;

Numata, Takanori ;

Kawaishi, Makoto ;

Hirano, Jun ;

Odaka, Makoto ;

Morikawa, Toshiaki ;

Nishimura, Stephen L. ;

Nakayama, Katsutoshi ;

Kuwano, Kazuyoshi .

ONCOIMMUNOLOGY, 2012, 1 (05) :630-641

[8] STRUCTURAL REMODELING OF CARDIAC MYOCYTES IN PATIENTS WITH ISCHEMIC CARDIOMYOPATHY [J].

GERDES, AM ;

KELLERMAN, SE ;

MOORE, JA ;

MUFFLY, KE ;

CLARK, LC ;

REAVES, PY ;

MALEC, KB ;

MCKEOWN, PP ;

SCHOCKEN, DD .

CIRCULATION, 1992, 86 (02) :426-430

[9] Repetitive stimulation of autophagy-lysosome machinery by intermittent fasting preconditions the myocardium to ischemia-reperfusion injury [J].

Godar, Rebecca J. ;

Ma, Xiucui ;

Liu, Haiyan ;

Murphy, John T. ;

Weinheimer, Carla J. ;

Kovacs, Attila ;

Crosby, Seth D. ;

Saftig, Paul ;

Diwan, Abhinav .

AUTOPHAGY, 2015, 11 (09) :1537-1560

[10] Insufficient Autophagy Contributes to Mitochondrial Dysfunction, Organ Failure, and Adverse Outcome in an Animal Model of Critical Illness [J].

Gunst, Jan ;

Derese, Inge ;

Aertgeerts, Annelies ;

Ververs, Eric-Jan ;

Wauters, Andy ;

Van den Berghe, Greet ;

Vanhorebeek, Ilse .

CRITICAL CARE MEDICINE, 2013, 41 (01) :182-194

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