P506Thymosin beta 4 in neovascularisation of the ischaemic heart post myocardial infarction
- Dube, K.N.
- Riley, P.R.
- Smart, N.S.
Purpose
The field of developmental biology has recently risen to the fore in informing cardiovascular regeneration; based on the simple premise that the same endogenous cardiac progenitor cells active during cardiovascular development can be re-activated with injury in the adult heart, to regenerate the damaged components of the heart. In the embryo, knockdown studies have demonstrated an essential requirement for Thymosin beta 4 (Tβ4), an actin monomer binding peptide, in epicardium-derived coronary vasculogenesis. In addition, Tβ4 treatment enhanced the heart's intrinsic neovascularisation post myocardial infarction (MI). However, it has not yet been established whether endogenous Tβ4 plays a role in the innate neovascular response following MI; an understanding of the endogenous response may enable the development of more efficient therapies for neovascular repair.
Methods and Results
Using a mouse model of coronary artery ligation we sought to investigate the role of Tβ4 in neovascularisation of the ischaemic heart post. Our results demonstrate that Tβ4 is upregulated post MI, particularly in the re-activated epicardium, and importantly, correlates with the extent of myocardial damage. Tβ4 knockout mice display a diminished epicardial activation and fewer new vessels post MI; these vessels, moreover, display inadequate smooth muscle support.
Conclusion
These findings suggest a role for endogenous Tβ4 in neovascularisation of the ischaemic heart, by enhancing epicardial activation and promoting mural cell development, in keeping with its known developmental roles. An understanding of these precise mechanisms is essential to augment the endogenous response to facilitate adequate revascularisation of the heart to salvage dying myocardium in the setting of cardiac ischaemia.