Endothelial-derived angiocrine factors as instructors of embryonic development

Abstract

Blood vessels are well-known to play roles in organ development and repair, primarily owing to their fundamental function in delivering oxygen and nutrients to tissues to promote their growth and homeostasis. Endothelial cells however are not merely passive conduits for carrying blood. There is now evidence that endothelial cells of the vasculature actively regulate tissue-specific development, morphogenesis and organ function, as well as playing roles in disease and cancer. Angiocrine factors are growth factors, cytokines, signaling molecules or other regulators produced directly from endothelial cells to instruct a diverse range of signaling outcomes in the cellular microenvironment, and are critical mediators of the vascular control of organ function. The roles of angiocrine signaling are only beginning to be uncovered in diverse fields such as homeostasis, regeneration, organogenesis, stem-cell maintenance, cell differentiation and tumour growth. While in some cases the specific angiocrine factor involved in these processes has been identified, in many cases the molecular identity of the angiocrine factor(s) remain to be discovered, even though the importance of angiocrine signaling has been implicated. In this review, we will specifically focus on roles for endothelial-derived angiocrine signaling in instructing tissue morphogenesis and organogenesis during embryonic and perinatal development.

Multi-Omics Profiling of Human Endothelial Cells from the Coronary Artery and Internal Thoracic Artery Reveals Molecular but Not Functional Heterogeneity

“…(5) resistance of arterial cell populations to oxidative stress, an imperative consequence of inflammation [92][93][94]; and (6) better vasoreactivity [95][96][97][98][99] and anti-thrombotic profile [100,101] of arterial ECs and VSMCs. As ECs play a key role in maintaining physiological vasodilation in response to blood pressure, have angiocrine function in terms of released extracellular vesicles and soluble factors, and ensure resistance of blood vessels to thrombosis [1][2][3][4][5], reciprocal and beneficial interactions between HCAECs and HITAECs might be of pathophysiological significance but largely depend on their heterogeneity. In this study, we aimed to perform an unbiased analysis of major proteins and global gene expression in HCAECs and HITAECs lysates by means of UHPLC-MS/MS and RNA sequencing, respectively.…”

“…Rather than being a simple semi-permeable barrier protecting the blood vessels from thrombosis, lipid retention, and mineral deposition, endothelial cells (ECs) deploy numerous angiocrine factors including cytokines, growth factors, vasoactive substances, and other signaling molecules regulating vascular and systemic homeostasis in a juxtacrine or paracrine manner [1][2][3][4][5]. Single-cell RNA sequencing has demonstrated an organ-specific pattern of EC differentiation [6][7][8][9] and molecular heterogeneity between arterial, capillary, venous, and lymphatic ECs [10][11][12][13][14][15].…”

Lineage Tracing Identifies Dynamic Contribution of Endothelial Cells to Cardiac Valve Mesenchyme During Development

“…11 Endothelial cells originating from the endocardial cushions are different from those within the heart chambers, expressing genes necessary for septum and valve development at different time patterns, such as genes encoding NFATc1 and vascular endothelial growth factor receptors. [21][22][23] These different gene express programs and the different signaling factors and receptors on the endocardial cushion determine the regional specificity of valve formation after EndoMT. In previous studies, a subpopulation of endocardial cells expressing NFATc1 did not undergo EndoMT but instead remained as a proliferating cell population.…”