Proteolytic remodelling of the extracellular matrix by pericytes

Pericytes (PCs) are perivascular cells that lie in close association with endothelial cells (ECs), with both cell types embedded within a shared basement membrane (BM), a specialised form of extracellular matrix (ECM). PCs regulate vascular integrity, angiogenesis and capillary blood flow and are capable of differentiating into other cell types including fibroblasts and smooth muscle cells. In recent years, a central role for PCs in regulating the development and maturation of the vasculature, maintaining tissue homeostasis and directing the pleiotropic remodelling of tissues during regeneration has emerged. Here, we review how PCs contribute to the synthesis and remodelling of the ECM in different pathophysiological conditions. Moreover, we provide an atlas of the PC matrisome, the complex of ECM molecules expressed by PCs, based on recent transcriptomics (in particular single-cell RNA sequencing) and proteomics datasets, with the caveat that such an entity does not exist in isolation due to the physical and paracrine interactions between PCs, ECs and other cell types. Understanding the role of PCs in modulating their microenvironment through active synthesis and degradation of specific matrisome components is essential to understand the role these plastic cells play in angiogenesis and in different pathologic conditions, including stroke, Alzheimer's disease and cancer.