Developmental angiocrine diversification of endothelial cells for organotypic regeneration

Adult organs are vascularized by specialized blood vessels. In addition to inter-organ vascular heterogeneity, each organ is arborized by structurally and functionally diversified populations of endothelial cells (ECs). The molecular pathways that are induced to orchestrate inter-and intra-organ vascular heterogeneity and zonation are shaped during development and fully specified postnatally. Notably, intra-organ specialization of ECs is associated with induction of angiocrine factors that guide cross-talk between ECs and parenchymal cells, establishing co-zonated vascular regions within each organ. In this review, we describe how microenvironmental tissue-specific biophysical, biochemical, immune, and inflammatory cues dictate the specialization of ECs with zonated functions. We delineate how physiological and biophysical stressors in the developing liver, lung, and kidney vasculature induce specialization of capillary beds. Deciphering mechanisms by which vascular microvasculature diversity is attained could set the stage for treating regenerative disorders and promote healing of organs without provoking fibrosis.

Automated summary

This review discusses the molecular pathways involved in orchestrating vascular heterogeneity and zonation within organs, as well as how physiological and biophysical stressors impact the specialization of capillary beds. The induction of angiocrine factors plays a key role in guiding communication between endothelial cells and parenchymal cells, establishing co-zonated vascular regions. Understanding the mechanisms behind microvascular diversity could have implications for treating regenerative disorders and promoting organ healing without causing fibrosis.