Molecular players in vascular development
Vessel formation entails a number of steps such as stabilisation, branching, remodelling and specialisation. One of the tissues participating in these processes is the vascular adventitia, the outermost layer of the vessel, which consists of fibroblasts and extra-cellular matrix (ECM). Recent evidence contradicts prior reports on the inertness of this structure, suggesting its active role in vascular development in health and disease. However, the processes that regulate the development, organisation and function of the embryonic adventitia remain elusive. To address this, scientists on the EU-funded PVA DEVELOPMENT (Identifying and characterizing regulators of primordial vascular adventitia development, organization and function) project set out to investigate the early events during vascular development that affect vascular adventitia and the ECM around the vessel. The work focused on the ECM remodelling enzyme family Lysyl oxidases (Lox), known for their role in vascular aneurysms in both humans and animals. By combining mouse genetics, ex vivo assays and biochemical experiments, researchers found that Lox enzymes are expressed in the endothelial cells, smooth muscle cells and adventitia of the vessels. To ablate the activity of these enzymes, they used the irreversible Lox-inhibitor β-aminoproprionitrile (BAPN). They discovered that Lox participated in endothelial sprouting and smooth muscle cell coating of the vessels. Further analysis by RNA sequencing enabled scientists to identify the specific pathways and genes downstream of Lox in vascular development and homeostasis. Given the role of the adventitia in various developmental and homeostatic processes including vessel tone regulation, remodelling, trafficking as well as vascular replenishing, the impact of the PVA DEVELOPMENT study is multifactorial. Overall, the reported findings provide a better understanding of Lox activities, unveiling for the first time their role in primordial vascular adventitia function.
Keywords
Development, vessel, adventitia, extracellular matrix, Lysyl oxidase, BAPN
