Insight into endothelial diversity
ECs line the inside of blood and lymphatic vessels forming an interface between the vessel wall and the circulating blood or lymph. They exhibit significant heterogeneity at the molecular, morphological and functional level due to both cell-intrinsic and -extrinsic factors. This heterogeneity may be the underlying cause of vascular bed-restricted disorders and may explain the side effects and limited success of general (anti-)angiogenic therapies. The scope of the EU-funded IMAGINED (Integrated multi-disciplinary approach to gain insight into endothelial diversity) project was to expand knowledge on EC diversity for the design of more specific vascular therapies. To achieve this, researchers followed a multi-disciplinary approach based on stem/progenitor cells and small animal models. Scientists analysed the genetic profile of arterial, venous and lymphatic ECs (macrovascular) as well as heart, brain and liver capillary ECs (microvascular). For each of these EC subtypes, they identified within these profiles a set of specific transcription factors. When they overexpressed arterial or heart EC-specific transcription factors in endothelial (progenitor) cells, they successfully obtained cells with the functional and molecular characteristics of the corresponding EC subtype. Furthermore, the consortium validated the role of two arterial and two cardiac endothelial transcription factors in murine and human tissues. Following manipulation of their expression in zebrafish and mice, they also demonstrated the functional importance of these transcription factors in the corresponding vascular beds. Taken together, the IMAGINED study provided fundamental insight into the molecular and functional characteristics of microvascular and macrovascular ECs. The identified differences could serve as the basis for the design of novel therapies, and for the future exploitation of the regenerative capacity of prespecialised EC progenitors to treat for example cardiac ischaemia.
Keywords
Endothelial cells, (anti-)angiogenic therapy, blood vessels, transcription factor
