The impact of perivascular cells on vascular morphogenesis and stability
Date
2022
DOI
Authors
Tefft, Juliann B.
Version
Embargo Date
2022-07-26,2022-07-26,2022-07-26,2022-07-26,2022-07-26,2022-07-26
OA Version
Citation
Abstract
The vasculature is a hierarchical system of blood vessels that regulates the transport of nutrients throughout the body. Vascular function relies not only on the endothelium that lines these vessels, but also on the cells which surround the vasculature. Here, we focus on two cell types – pericytes, which are embedded within the vascular basement membrane, and fibroblasts, which reside in the surrounding tissue stroma. In the vasculature, these perivascular cells work in concert with the endothelium to heal injuries and maintain vascular barrier. In Chapter 2, we focus on the interaction of endothelial cells and fibroblasts. During wound healing, fibroblasts and endothelial cells must coordinate to revascularize the injured region, and dysregulation of this process can result in chronic wounds. We develop an in vitro model of vascular wound healing and investigate how endothelial cells and fibroblasts interact during this healing process. We find that fibroblasts are critical to the healing response by contracting the wound and depositing extracellular matrix, and these actions are required before endothelial cells can enter the injury site. In Chapter 3, we discuss the role of heterotypic communication between the endothelium and pericytes. Pericyte interaction with the endothelium helps restrict the leak of fluids and proteins from the vasculature. In pathological conditions, the connection of pericytes with the endothelium is often disrupted, leading to detrimental vascular leak, however, much is still unknown about the precise impact of pericytes on the endothelium. We investigate the role of Notch signaling between endothelial cells and pericytes on regulating endothelial junctions and identify that heterotypic crosstalk between Notch receptors in the opposing cells contributes to the stability of endothelial junctions. Together, this work provides new insights into the dynamic coordination between endothelial cells and perivascular cells and how these heterotypic interactions impact vascular function.