Abstract
BackgroundThe epicardium has key functions during myocardial development, by contributing to the formation of coronary endothelial and smooth muscle cells, cardiac fibroblasts, and potentially cardiomyocytes. The epicardium plays a morphogenetic role by emitting signals to promote and maintain cardiomyocyte proliferation. In a regenerative context, the adult epicardium might comprise a progenitor cell population that can be induced to contribute to cardiac repair. Although some genes involved in epicardial function have been identified, a detailed molecular profile of epicardial gene expression has not been available.MethodologyUsing laser capture microscopy, we isolated the epicardial layer from the adult murine heart before or after cardiac infarction in wildtype mice and mice expressing a transgenic IGF-1 propeptide (mIGF-1) that enhances cardiac repair, and analyzed the transcription profile using DNA microarrays.Principal FindingsExpression of epithelial genes such as basonuclin, dermokine, and glycoprotein M6A are highly enriched in the epicardial layer, which maintains expression of selected embryonic genes involved in epicardial development in mIGF-1 transgenic hearts. After myocardial infarct, a subset of differentially expressed genes are down-regulated in the epicardium representing an epicardium-specific signature that responds to injury.ConclusionThis study presents the description of the murine epicardial transcriptome obtained from snap frozen tissues, providing essential information for further analysis of this important cardiac cell layer.
Highlights
The epicardium is a single epithelial cell layer overlying the vertebrate heart
The epicardium does retain some capability to be involved in repair processes in mammals, in that for example Thymosin beta-4 can activate adult epicardial cells [9] acting through reactivation of embryonic signalling pathways [10]
In newer studies cardiomyocyte progenitors were cotransplanted with epicardiumderived cells (EPDCs) into infarcted myocardial tissues, which improved functional repair when compared to single cell type supplementation [14]
Summary
The epicardium is a single epithelial cell layer overlying the vertebrate heart. It derives from the proepicardium that gives rise to the vasculature and interstitial cells of the heart during embryogenesis, a process that is mandatory for normal development [1,2,3,4]. The zebrafish epicardium supports cardiac regeneration through epithelial to mesenchymal transition (EMT) and subsequent migration into the myocardium to form new vasculature [8] In mammals, these regenerative processes are not active to the degree that they support recovery of infarcted myocardial tissue. The epicardium does retain some capability to be involved in repair processes in mammals, in that for example Thymosin beta-4 can activate adult epicardial cells [9] acting through reactivation of embryonic signalling pathways [10] This thymosin mediated activation of epicardial cells can support revascularization of the injured mammalian heart by forming endothelial and vascular smooth muscle cells [11]. Some genes involved in epicardial function have been identified, a detailed molecular profile of epicardial gene expression has not been available
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