The reason why a hypoxic tumor forms its own vasculature, mainly through the secretion of the Vascular Endothelial Growth Factor (VEGF), whereas an ischemic heart cannot, still remains obscure. We hypothesize that cardiac endothelial cells lose their capacity to proliferate soon after birth, similar to what happens to mammalian cardiomyocytes.
By using transgenic fate mapping, we show that cardiac endothelial cells do not respond to pro-angiogenic stimuli, i.e. VEGF overexpression and cancer cells. While they do sense the stimulus, they fail to form elongated vascular structures. We are currently investigating the mechanisms that halt the angiogenic potential of endothelial cells in the post-natal heart, with the aim of developing novel therapeutic opportunities to promote angiogenesis in the ischemic heart.