Thymosin β4 induces adult epicardial progenitor mobilization and neovascularization

Nicola Smart, Catherine A. Risebro, Athalie A. D. Melville, Kelvin Moses, Robert J. Schwartz, Kenneth R. Chien and Paul R. Riley ()
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Nicola Smart: UCL Institute of Child Health
Catherine A. Risebro: UCL Institute of Child Health
Athalie A. D. Melville: UCL Institute of Child Health
Kelvin Moses: Baylor College of Medicine
Robert J. Schwartz: Baylor College of Medicine
Kenneth R. Chien: Harvard Medical School, and the Harvard Stem Cell Institute
Paul R. Riley: UCL Institute of Child Health

Nature, 2007, vol. 445, issue 7124, 177-182

Abstract: Abstract Cardiac failure has a principal underlying aetiology of ischaemic damage arising from vascular insufficiency. Molecules that regulate collateral growth in the ischaemic heart also regulate coronary vasculature formation during embryogenesis. Here we identify thymosin β4 (Tβ4) as essential for all aspects of coronary vessel development in mice, and demonstrate that Tβ4 stimulates significant outgrowth from quiescent adult epicardial explants, restoring pluripotency and triggering differentiation of fibroblasts, smooth muscle cells and endothelial cells. Tβ4 knockdown in the heart is accompanied by significant reduction in the pro-angiogenic cleavage product N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP). Although injection of AcSDKP was unable to rescue Tβ4 mutant hearts, it significantly enhanced endothelial cell differentiation from adult epicardially derived precursor cells. This study identifies Tβ4 and AcSDKP as potent stimulators of coronary vasculogenesis and angiogenesis, and reveals Tβ4-induced adult epicardial cells as a viable source of vascular progenitors for continued renewal of regressed vessels at low basal level or sustained neovascularization following cardiac injury.

Date: 2007
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DOI: 10.1038/nature05383

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