Thymosin beta4 facilitates epicardial neovascularization of the injured adult heart.
Ischemic heart disease complicated by coronary artery occlusion causes myocardial infarction (MI), which is the major cause of morbidity and mortality in humans (http://www.who.int/cardiovascular_diseases/resources/atlas/en/index.html). After MI the human heart has an impaired capacity to regenerate and, despite the high prevalence of cardiovascular disease worldwide, there is currently only limited insight into how to stimulate repair of the injured adult heart from its component parts. Efficient cardiac regeneration requires the replacement of lost cardiomyocytes, formation of new coronary blood vessels, and appropriate modulation of inflammation to prevent maladaptive remodeling, fibrosis/scarring, and consequent cardiac dysfunction. Here we show that thymosin beta4 (Tbeta4) promotes new vasculature in both the intact and injured mammalian heart. We demonstrate that limited EPDC-derived endothelial-restricted neovascularization constitutes suboptimal "endogenous repair," following injury, which is significantly augmented by Tbeta4 to increase and stabilize the vascular plexus via collateral vessel growth. As such, we identify Tbeta4 as a facilitator of cardiac neovascularization and highlight adult EPDCs as resident progenitors which, when instructed by Tbeta4, have the capacity to sustain the myocardium after ischemic damage.
Molecular Medicine Unit, UCL Institute of Child Health, London, UK.
Nicola
N
Smart
Catherine A
CA
Risebro
James E
JE
Clark
Elisabeth
E
Ehler
Lucile
L
Miquerol
Alex
A
Rossdeutsch
Michael S
MS
Marber
Paul R
PR
Riley
D000328:Adult; D006801:Humans; D009203:Myocardial Infarction / Q000150:complications* / Q000235:genetics / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000150:complications* / Q000235:genetics; D009206:Myocardium; D032383:Myocytes, Cardiac; D009389:Neovascularization, Pathologic / Q000150:complications* / Q000235:genetics; D012038:Regeneration / Q000235:genetics; D013947:Thymosin / Q000502:physiology*; D014945:Wound Healing / Q000235:genetics; D000099201:Thymosin beta(4)
D013947:Thymosin; D000099201:Thymosin beta(4)