Document Detail

Overexpression of human amyloidogenic light chains causes heart failure in embryonic zebrafish: a preliminary report.
MedLine Citation:
PMID:  23126591     Owner:  NLM     Status:  In-Data-Review    
AL cardiomyopathy leading to heart failure (HF) represents a significant cause of morbidity and mortality in systemic amyloidosis. However, the paucity of robust in vivo models of AL-induced cardiac dysfunction has limited our ability to probe the mechanisms of AL heart disease. To address this problem, we have developed a model of AL HF in zebrafish embryos by injection of in vitro transcribed mRNA encoding amyloidogenic light chain (aLC) into fertilized oocytes. We demonstrate that expression of aLC causes cardiomyopathy in developing zebrafish without significantly impairing extracardiac development. The cardiac ventricle of embryos expressing aLC exhibit impaired contractility, smaller size, and increased myocardial thickness which result in congestion and edema, features paralleling the clinical manifestations of amyloid cardiomyopathy. Phosphorylated p38, a marker of oxidative stress, was increased in response to aLC expression. No evidence of amyloid fibril deposition was identified. Thus, expression of aLC mRNA in zebrafish results in cardio toxic effects without fibril deposition. This is consistent with prior evidence indicating that aLC oligomers mediate cardiac dysfunction in vitro. This model will allow exploration of amyloid pathophysiology and testing of interventions to reduce and reverse the deleterious effects of amyloidosis on myocardial function.
Jordan T Shin; Jennifer E Ward; Patricia A Collins; Matthew Dai; Hannah L Semigran; Marc J Semigran; David C Seldin
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis     Volume:  19     ISSN:  1744-2818     ISO Abbreviation:  Amyloid     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-06     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9433802     Medline TA:  Amyloid     Country:  England    
Other Details:
Languages:  eng     Pagination:  191-6     Citation Subset:  IM    
Cardiology Division.
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