Regulation of endothelial cell differentiation in embryonic vascular development and its therapeutic potential in cardiovascular diseases

During vertebrate development, the cardiovascular system begins operating earlier than any other organ in the embryo. Endothelial cell (EC) forms the inner lining of blood vessels, and its extensive proliferation and migration are requisite for vasculogenesis and angiogenesis. Many aspects of cellular biology are involved in vasculogenesis and angiogenesis, including the tip versus stalk cell specification. Recently, epigenetics has attracted growing attention in regulating embryonic vascular development and controlling EC differentiation. Some proteins that regulate chromatin structure have been shown to be directly implicated in human cardiovascular diseases. Additionally, the roles of important EC signaling such as vascular endothelial growth factor and its receptors, angiopoietin-1 and tyrosine kinase containing immunoglobulin and epidermal growth factor homology domain-2, and transforming growth factor-β in EC differentiation during embryonic vasculature development are briefly discussed in this review. Recently, the transplantation of human induced pluripotent stem cell (iPSC)-ECs are promising approaches for the treatment of ischemic cardiovascular disease including myocardial infarction. Patient-specific iPSC-derived EC is a potential new target to study differences in gene expression or response to drugs. However, clinical application of the iPSC-ECs in regenerative medicine is often limited by the challenges of maintaining cell viability and function. Therefore, novel insights into the molecular mechanisms underlying EC differentiation might provide a better understanding of embryonic vascular development and bring out more effective EC-based therapeutic strategies for cardiovascular diseases.