The zebrafish heart regenerates after cryoinjury-induced myocardial infarction

被引:293
作者
Chablais, Fabian [1 ,3 ]
Veit, Julia [2 ]
Rainer, Gregor [2 ]
Jazwinska, Anna [1 ,3 ]
机构
[1] Univ Fribourg, Unit Anat, Dept Med, CH-1700 Fribourg, Switzerland
[2] Univ Fribourg, Unit Physiol, Dept Med, CH-1700 Fribourg, Switzerland
[3] Univ Fribourg, Dept Biol, Unit Zool, CH-1700 Fribourg, Switzerland
来源
BMC DEVELOPMENTAL BIOLOGY | 2011年 / 11卷
基金
瑞士国家科学基金会;
关键词
CARDIAC REGENERATION; EXTRACELLULAR-MATRIX; TENASCIN-C; MATRICELLULAR PROTEINS; NEWT CARDIOMYOCYTES; FIN REGENERATION; CELL; DISEASE; MODEL; PROLIFERATION;
D O I
10.1186/1471-213X-11-21
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background: In humans, myocardial infarction is characterized by irreversible loss of heart tissue, which becomes replaced with a fibrous scar. By contrast, teleost fish and urodele amphibians are capable of heart regeneration after a partial amputation. However, due to the lack of a suitable infarct model, it is not known how these animals respond to myocardial infarction. Results: Here, we have established a heart infarct model in zebrafish using cryoinjury. In contrast to the common method of partial resection, cryoinjury results in massive cell death within 20% of the ventricular wall, similar to that observed in mammalian infarcts. As in mammals, the initial stages of the injury response include thrombosis, accumulation of fibroblasts and collagen deposition. However, at later stages, cardiac cells can enter the cell cycle and invade the infarct area in zebrafish. In the subsequent two months, fibrotic scar tissue is progressively eliminated by cell apoptosis and becomes replaced with a new myocardium, resulting in scarless regeneration. We show that tissue remodeling at the myocardial-infarct border zone is associated with accumulation of Vimentin-positive fibroblasts and with expression of an extracellular matrix protein Tenascin-C. Electrocardiogram analysis demonstrated that the reconstitution of the cardiac muscle leads to the restoration of the heart function. Conclusions: We developed a new cryoinjury model to induce myocardial infarction in zebrafish. Although the initial stages following cryoinjury resemble typical healing in mammals, the zebrafish heart is capable of structural and functional regeneration. Understanding the key healing processes after myocardial infarction in zebrafish may result in identification of the barriers to efficient cardiac regeneration in mammals.
引用
收藏
页数:13
相关论文
共 47 条
[1]   From fish to amphibians to mammals: in search of novel strategies to optimize cardiac regeneration [J].
Ausoni, Simonetta ;
Sartore, Saverio .
JOURNAL OF CELL BIOLOGY, 2009, 184 (03) :357-364
[2]   REPAIR AND REORGANIZATION OF MINCED CARDIAC-MUSCLE IN ADULT NEWT (NOTOPHTHALMUS-VIRIDESCENS) [J].
BADER, D ;
OBERPRILLER, JO .
JOURNAL OF MORPHOLOGY, 1978, 155 (03) :349-357
[3]   Heterogeneous proliferative potential in regenerative adult newt cardiomyocytes [J].
Bettencourt-Dias, M ;
Mittnacht, S ;
Brockes, JP .
JOURNAL OF CELL SCIENCE, 2003, 116 (19) :4001-4009
[4]   Cardiovascular regeneration in non-mammalian model systems: What are the differences between newts and man? [J].
Borchardt, Thilo ;
Braun, Thomas .
THROMBOSIS AND HAEMOSTASIS, 2007, 98 (02) :311-318
[5]   Matricellular proteins: extracellular modulators of cell function [J].
Bornstein, P ;
Sage, EH .
CURRENT OPINION IN CELL BIOLOGY, 2002, 14 (05) :608-616
[6]   High-throughput assay for small molecules that modulate zebrafish embryonic heart rate [J].
Burns, CG ;
Milan, DJ ;
Grande, EJ ;
Rottbauer, W ;
MacRae, CA ;
Fishman, MC .
NATURE CHEMICAL BIOLOGY, 2005, 1 (05) :263-264
[7]   Structural and functional characterisation of cardiac fibroblasts [J].
Camelliti, P ;
Borg, TK ;
Kohl, P .
CARDIOVASCULAR RESEARCH, 2005, 65 (01) :40-51
[8]   IGF signaling between blastema and wound epidermis is required for fin regeneration [J].
Chablais, Fabian ;
Jazwinska, Anna .
DEVELOPMENT, 2010, 137 (06) :871-879
[9]   Cytoskeletal and cellular adhesion proteins in zebrafish (Danio rerio) myogenesis [J].
Costa, ML ;
Escaleira, R ;
Manasfi, M ;
de Souza, LF ;
Mermelstein, CS .
BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH, 2003, 36 (08) :1117-1120
[10]   The extracellular matrix as a modulator of the inflammatory and reparative response following myocardial infarction [J].
Dobaczewski, Marcin ;
Gonzalez-Quesada, Carlos ;
Frangogiannis, Nikolaos G. .
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2010, 48 (03) :504-511