The pericyte microenvironment during vascular development

Abstract

Vascular pericytes provide critical contributions to the formation and integrity of the blood vessel wall within the microcirculation. Pericytes maintain vascular stability and homeostasis by promoting endothelial cell junctions and depositing extracellular matrix (ECM) components within the vascular basement membrane, among other vital functions. As their importance in sustaining microvessel health within various tissues and organs continues to emerge, so does their role in a number of pathological conditions including cancer, diabetic retinopathy, and neurological disorders. Here, we review vascular pericyte contributions to the development and remodeling of the microcirculation, with a focus on the local microenvironment during these processes. We discuss observations of their earliest involvement in vascular development and essential cues for their recruitment to the remodeling endothelium. Pericyte involvement in the angiogenic sprouting context is also considered with specific attention to crosstalk with endothelial cells such as through signaling regulation and ECM deposition. We also address specific aspects of the collective cell migration and dynamic interactions between pericytes and endothelial cells during angiogenic sprouting. Lastly, we discuss pericyte contributions to mechanisms underlying the transition from active vessel remodeling to the maturation and quiescence phase of vascular development.

Postnatal development of cerebrovascular structure and the neurogliovascular unit

“…However, these opposing views come from diverse model systems and organs, and likely differ in various angiogenic contexts. Recent data from Payne et al reveal a potential middle ground where pericyte and endothelial tip cells co‐migrate, taking turns to lead the new capillary sprout (Payne et al, ). The relative position of pericytes and endothelial cells was hypothesized to be dependent upon fluctuations in the availability of ligands such as PDGF‐BB at the angiogenic front.…”

Pericytes in Vascular Development

“…Thus, this unique configuration of ECM proteins (e.g., Type IV Collagen (Col-IV), laminins, perlecan) surrounding microvascular endothelia and pericytes can offer another criteria for their identification [32]. Ultimately, pericytes are the best identified through a combination of pericyte and endothelial markers, rigorous assessment of their morphology (which may include some slight heterogeneity [33,34]), and their location within microvascular networks. Coupling these benchmarks with next generation sequencing approaches and single-cell analysis will sharpen existing pericyte-specific tools, and allow greater insight into critical questions such as when terminally differentiated pericytes first emerge during embryonic development and how they expand their coverage along the rapidly developing vasculature.…”

Pericytes Relationship with Cancer Stem Cells in the Colon

“…They are involved in the preservation of vascular stability and homeostasis including, but not restricted to, maintenance of vessel structure, regulation of blood flow, vascular permeability, and remodeling of the extracellular matrix (ECM). They are also essential for normal blood vessel development [14]. Unfortunately, in the case of abnormal pericyte function or the loss of numbers of pericytes can be associated with some pathologies such as fibrosis; ischemic organ failure; diabetesrelated complications; pulmonary hypertension; Alzheimer disease; and cancer promoting tumor growth, metastasis, and angiogenesis.…”