Abstract
Unlike mammals, adult zebrafish hearts retain a remarkable capacity to regenerate after injury. Since regeneration shares many common molecular pathways with embryonic development, we investigated myocardial remodeling genes and pathways by performing a comparative transcriptomic analysis of zebrafish heart regeneration using a set of known human hereditary heart disease genes related to myocardial hypertrophy during development. We cross-matched human hypertrophic cardiomyopathy-associated genes with a time-course microarray dataset of adult zebrafish heart regeneration. Genes in the expression profiles that were highly elevated in the early phases of myocardial repair and remodeling after injury in zebrafish were identified. These genes were further analyzed with web-based bioinformatics tools to construct a regulatory network revealing potential transcription factors and their upstream receptors. In silico functional analysis of these genes showed that they are involved in cardiomyocyte proliferation and differentiation, angiogenesis, and inflammation-related pathways. The regulatory network indicated that β-2- microglobulin-mediated signaling may play an important role in myocardial remodeling after injury. This novel cross-species bioinformatics approach to uncover key modulators of zebrafish heart regeneration through human hereditary disease genomic analysis could greatly facilitate the understanding of the evolutionarily conserved cardiac remodeling process.