VASC-GEN · Endoglin-Mediated Vascular Regeneration to Promote Heart Repair

The standard emergency treatment for myocardial infarction (MI) has so improved over the last decade that most patients survive. However, many of these patients still go on to develop heart failure over the subsequent months and years. Vascular regeneration using autologous cells, if given at an early stage in patient treatment, can promote cardiac repair following MI and reduce the adverse cardiac remodelling that leads to heart failure. However, clinical trials have clearly shown that currently available therapies provide only minor improvement in heart function and require significant refinement before they become a useful clinical treatment. Further basic research is urgently required to advance these vascular regeneration therapies to improve patient outcomes. This project builds on the recent finding that cardiac stem cell populations expressing the TGFbeta/BMP co-receptor endoglin promotes angiogenesis in the myocardial infarct region with greater efficiency than endoglin-depleted cells. As donor cells are rarely retained after stem cell transfer to the heart, this finding strongly suggests that endoglin-positive cardiac stem cells have a pro-angiogenic secretome, that is lost in the absence of endoglin. This project will take advantage of this discovery and will use mouse models of acute MI to determine the most potent combinations of pro-angiogenic protein factors that lead to cardiac vascular regeneration in vivo. By developing optimal conditions for therapeutic angiogenesis we anticipate being able to significantly reduce myocyte loss following acute MI and decrease the risk of subsequent heart failure.""