Abstract
The transcription factor Islet‐1 marks a progenitor cell population of the second heart field during cardiogenesis. In the adult heart Islet‐1 expression is limited to the sinoatrial node, the ventricular outflow tract, and parasympathetic ganglia. The regenerative effect in the injured mouse ventricle of thymosin beta‐4 (TB4), a 43‐aminoacid peptide, was associated with increased Islet‐1 immunostaining, suggesting the induction of an Islet‐1‐positive progenitor state by TB4. Here we aimed to reassess this effect in a genetic model. Mice from the reporter mouse line Isl1‐nLacZ were primed with TB4 and subsequently underwent myocardial infarction. Islet‐1 expression was assessed 2, 7, and 14 days after infarction. We detected only a single Islet‐1+ cell in 8 TB4 treated and infarcted hearts which located outside of the sinoatrial node, the outflow tract or cardiac ganglia (in ~2500 sections). Two cells were identified in 5 control infarcted hearts. TB4 did not induce LacZ positivity in ventricular explants cultures of Isl1‐nLacZ mice nor did it affect the density of LacZ+ cells in explant cultures of nLacZ+ regions of the heart. In summary, we found no evidence that TB4 reactivates Islet‐1 expression in adult mouse ventricle.
Highlights
One possible treatment strategy aims at stimulating proliferation and differentiation of endogenous progenitor cells in the adult heart
Islet-1 expression in the adult heart is limited to very distinct regions[7,8]: cells of the outflow tract and parasympathetic ganglia as well as the sinoatrial
We identified 3 nLacZ+ cells that could not be ascribed to any of these 3 structures (Figure 3B): a single cell was detected in a thymosin beta-4 (TB4)-treated Isl1-nLacZ mouse 14 days after left anterior descending artery (LAD)-ligation
Summary
Regenerative strategies might represent new therapeutic approaches to heart failure, which is still the leading cause of death in the western world.[1]. During cardiac development Islet-1 marks a progenitor cell population of the second heart field. These Islet-1+ cells are capable of differentiating to cardiomyocytes, smooth muscle cells, and endothelial cells and contribute to the right ventricle, the right atrium and the outflow tract.[3-5]. TB4 improved vasculogenesis, reduced infarct size, prevented ventricular rupture and improved left ventricular function after myocardial infarction It extended the time window for cardiac regeneration after birth and amplified the effect of Gata[4], Mef2c, and Tbx[5] to transdifferentiate fibroblasts to cardiomyocytes.[19-26]. Given the limited specificity of immunolabeling in histological preparations we set out to reevaluate the effect of TB4 on distribution and role of Islet-1+ cells after injury using a genetically defined model
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