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Cardiac compensation for lack of trabeculae in ErbB2‐deficient zebrafish (648.3)
Author(s) -
Fleming Nicole,
Samsa Leigh Ann,
Liu Jiandong
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.648.3
Subject(s) - zebrafish , cardiac function curve , pressure overload , sarcomere , heart failure , heart development , microbiology and biotechnology , medicine , phenotype , muscle hypertrophy , biology , embryo , cardiology , endocrinology , anatomy , embryonic stem cell , myocyte , cardiac hypertrophy , genetics , gene
Congenital heart disease (CHD) is one of the major causes of birth defects among infants in the United States. CHD can be characterized by malformations during heart development. Initially, the heart is a smooth, linear tube of cardiomyocytes lined with specialized endothelial cells. Following cardiac looping, the heart chambers undergo dramatic changes in chamber topology, most notably the formation of luminal, muscular protrusions called trabeculae. While altered trabeculation leads to severe cardiac defects, complete failure to form trabeculae results in embryonic lethality in human, mouse, chick, and zebrafish due to cardiovascular failure. We hypothesize that cardiac trabeculation is critical for cardiac function in the developing heart. Due to their external fertilization and genetic tractability, we use the zebrafish embryo to observe trabeculation. Zebrafish cardiac trabeculation requires both genetic and non‐genetic mediators: requiring input from the Neuregulin/ErbB2 signaling pathway and hemodynamic forces, respectively. To understand the cellular mechanism of progressive cardiac dysfunction in the absence of trabeculae, we inhibited ErbB2 signaling in the zebrafish model. Preliminary data indicates increased compact myocardial thickness (2.09 ± 0.19 μm in DMSO treated fish vs. 3.96 ± 0.35 μm in ErbB2‐inhibitor treated fish; p <0.05) and sarcomere length (1.30 ± 0.15 μm in DMSO treated fish vs. 1.92 ± 0.18 μm in ErbB2‐inhibitor treated fish; p <0.001), a phenotype reminiscent of pressure overload‐stimulated cardiac hypertrophy. This compensatory mechanism suggests that trabeculae may play a role in optimizing chamber topology for efficient cardiac function. Grant Funding Source : Supported by: Initiative for Maximizing Student Diversity (IMSD): 5R25GM055336 and BBSP