Thymosin β-4 Is Essential for Coronary Vessel Development and Promotes Neovascularization via Adult Epicardium

:  Ischemic heart disease leading to myocardial infarction causes irreversible cell loss and scarring and is a major cause of morbidity and mortality in humans. Significant effort in the field of cardiovascular medicine has been invested in the search for adult cardiac progenitor cells that may repl...

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Veröffentlicht in:Annals of the New York Academy of Sciences 2007-09, Vol.1112 (1), p.171-188
Hauptverfasser: SMART, NICOLA, RISEBRO, CATHERINE A., MELVILLE, ATHALIE A. D., MOSES, KELVIN, SCHWARTZ, ROBERT J., CHIEN, KENNETH R., RILEY, PAUL R.
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container_issue 1
container_start_page 171
container_title Annals of the New York Academy of Sciences
container_volume 1112
creator SMART, NICOLA
RISEBRO, CATHERINE A.
MELVILLE, ATHALIE A. D.
MOSES, KELVIN
SCHWARTZ, ROBERT J.
CHIEN, KENNETH R.
RILEY, PAUL R.
description :  Ischemic heart disease leading to myocardial infarction causes irreversible cell loss and scarring and is a major cause of morbidity and mortality in humans. Significant effort in the field of cardiovascular medicine has been invested in the search for adult cardiac progenitor cells that may replace damaged muscle cells and/or contribute to new vessel formation (neovascularization) and in the identification of key factors, which may induce such progenitor cells to contribute to myocardial repair and collateral vessel growth. We recently demonstrated that the actin monomer‐binding protein, thymosin β‐4 (Tβ‐4), when secreted from the myocardium provides a paracrine stimulus to the cells of the epicardium‐derived cells (EPDCs) to promote their inward migration and differentiation into endothelial and smooth muscle cells to form the coronary vasculature. Translating this essential role for Tβ‐4 in coronary vessel development to the adult, we found that treatment of cultured adult explants with Tβ‐4 stimulated extensive outgrowth of epicardin‐positive epicardial cells, which, as they migrated away from the explant, differentiated into procollagen type I, SMαA, and Flk1‐positive cells indicative of fibroblasts, smooth muscle, and endothelial cells; thus releasing the adult epicardium from a quiescent state and restoring pluripotency. The ability of Tβ‐4 to promote coronary vessel development and potentially induce new vasculature in the adult is essential for cardiomyocyte survival and could contribute significantly toward the reported Tβ4‐induced cardioprotection and repair in the adult heart. Tβ‐4 is currently subject to multicenter phase 1 clinical trials for treatment of cardiovascular disease (http://www.regenerx.com), therefore, insight into the repair mechanism(s) induced by Tβ‐4 is an essential step toward harnessing therapeutic survival, migration, and repair properties of the peptide in the context of acute myocardial damage.
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Significant effort in the field of cardiovascular medicine has been invested in the search for adult cardiac progenitor cells that may replace damaged muscle cells and/or contribute to new vessel formation (neovascularization) and in the identification of key factors, which may induce such progenitor cells to contribute to myocardial repair and collateral vessel growth. We recently demonstrated that the actin monomer‐binding protein, thymosin β‐4 (Tβ‐4), when secreted from the myocardium provides a paracrine stimulus to the cells of the epicardium‐derived cells (EPDCs) to promote their inward migration and differentiation into endothelial and smooth muscle cells to form the coronary vasculature. Translating this essential role for Tβ‐4 in coronary vessel development to the adult, we found that treatment of cultured adult explants with Tβ‐4 stimulated extensive outgrowth of epicardin‐positive epicardial cells, which, as they migrated away from the explant, differentiated into procollagen type I, SMαA, and Flk1‐positive cells indicative of fibroblasts, smooth muscle, and endothelial cells; thus releasing the adult epicardium from a quiescent state and restoring pluripotency. The ability of Tβ‐4 to promote coronary vessel development and potentially induce new vasculature in the adult is essential for cardiomyocyte survival and could contribute significantly toward the reported Tβ4‐induced cardioprotection and repair in the adult heart. Tβ‐4 is currently subject to multicenter phase 1 clinical trials for treatment of cardiovascular disease (http://www.regenerx.com), therefore, insight into the repair mechanism(s) induced by Tβ‐4 is an essential step toward harnessing therapeutic survival, migration, and repair properties of the peptide in the context of acute myocardial damage.</abstract><cop>Malden, USA</cop><pub>Blackwell Publishing Inc</pub><pmid>17495252</pmid><doi>10.1196/annals.1415.000</doi><tpages>18</tpages></addata></record>
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subjects Animals
Coronary Disease - prevention & control
Coronary Vessels - growth & development
Coronary Vessels - physiology
epicardium
Heart - drug effects
Heart - growth & development
Heart - physiology
Mice
myocardium
neovascularization
Neovascularization, Pathologic - prevention & control
Pericardium - drug effects
Pericardium - physiology
progenitors
regeneration
therapeutic repair
thymosin
Thymosin - physiology
title Thymosin β-4 Is Essential for Coronary Vessel Development and Promotes Neovascularization via Adult Epicardium
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