Community Research and Development Information Service - CORDIS


VASC-GEN Result In Brief

Project ID: 329813
Funded under: FP7-PEOPLE
Country: United Kingdom

Repairing the heart from within

Myocardial infarction (MI), also known as heart attack, is the major cause of death worldwide. The development of regenerative therapies could significantly improve patient outcome.
Repairing the heart from within
Although standard emergency treatment of MI has improved over the years and a substantial number of patients survive, they eventually develop heart failure. To prevent adverse cardiac remodelling and promote cardiac repair as soon as possible after MI, it is vital to induce vascular regeneration and supply oxygen to the infarcted region.

In this context, autologous cells present promising candidates but clinical trials' results emphasise the need for significant refinement before they become a useful clinical treatment. Accumulating evidence suggests that a heterogeneous cardiac stem cell population known as the cardiosphere-derived cells (CDCs) have the potential to rescue heart function. These cells function by releasing factors that enhance various repair processes including new vessel formation (angiogenesis). However, this ability is strongly associated with the presence of the endoglin gene.

Scientists on the EU-funded VASC-GEN (Endoglin-mediated vascular regeneration to promote heart repair) project wished to delineate the role of the endoglin gene in the function of CDCs. For this purpose, they analysed the factors secreted by endoglin positive CDCs or cells lacking endoglin. They also examined the influence of CDCs with and without endoglin on cardiac repair after MI in a mouse model.

Project results indicated that endoglin expression in CDCs led to paracrine effects that enhanced endothelial cell proliferation and migration in vitro. Various angiogenesis-related proteins including members of the TGFbeta signalling pathway mediated these effects. Mass spectrometry analysis further pinpointed a deregulation in extracellular matrix proteins as well as in members of the SMAD and the platelet derived growth factor binding families in the absence of endoglin. When administered in vivo, endoglin positive CDCs exhibited an improved pro-angiogenic effect with the formation of new functional vessels.

Taken together, the results of the VASC-GEN project emphasised the capacity of CDCs to induce angiogenesis and underscored the significance of the endoglin gene. Long-term the identification of pro-angiogenic factors in the CDC secretome will provide a more controlled strategy for treating ischaemic disease.

Related information


Myocardial infarction, regenerative therapies, cardiosphere-derived cells, angiogenesis, endoglin
Record Number: 181161 / Last updated on: 2016-05-10
Domain: Biology, Medicine