Abstract
The epicardium, a mesothelial layer that envelops vertebrate hearts, has become a therapeutic target in cardiac repair strategies because of its vital role in heart development and cardiac injury response. Epicardial cells serve as a progenitor cell source and signaling center during both heart development and regeneration. The importance of the epicardium in cardiac repair strategies has been reemphasized by recent progress regarding its requirement for heart regeneration in zebrafish, and by the ability of patches with epicardial factors to restore cardiac function following myocardial infarction in mammals. The live surveillance of epicardial development and regeneration using zebrafish has provided new insights into this topic. In this review, we provide updated knowledge about epicardial development and regeneration.
Highlights
Heart disease is a leading cause of death worldwide
Studies using zebrafish and mice have shown that the epicardium serves as a source of paracrine signals (including retinoic acid (RA) and neuregulin 1 (Nrg1)) and extracellular matrix (ECM) for CM survival or division [5,6,7,8,9,10,11,12,13]
Studies of epicardial regeneration have brought several conceptual advances that affect how we think of tissue regeneration
Summary
In the US alone, an estimated 900,000 people suffer a myocardial infarction (MI) each year [1], leading to cardiac muscle damage. The adult mammalian heart has a limited ability to regenerate damaged cardiac muscle after heart attack [2]. The epicardium is critical for heart development by serving as a progenitor pool and signaling center [3,4]. The epicardium serves as a source of paracrine signals for cardiomyocyte (CM) survival or division, as a supply of perivascular components and possibly other cell types such as CMs, and as a mediator of inflammation [5,6,7,8,9,10,11,12,13]. To include the epicardium in cardiac repair strategies, we need a comprehensive understanding of its role in heart development and regeneration. We discuss the most recent progress and debates from the last few years, especially the new findings derived from live imaging in zebrafish embryos and explant culturing of adult zebrafish hearts
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