The role of pericyte detachment in vascular rarefaction

Abstract

Background: Pericytes surround endothelial cells at the perivascular interface. Signaling between endothelial cells and pericytes is crucial for capillary homeostasis, as pericytes stabilize vessels and regulate many microvascular functions. Recently it has been shown that pericytes are able to detach from the vascular wall and contribute to fibrosis by becoming scar-forming myofibroblasts in many organs including the kidney. At the same time, the loss of pericytes within the perivascular compartment results in vulnerable capillaries which are prone to instability, pathological angiogenesis, and, ultimately, rarefaction.

Aims: This review will give an overview of pericyte-endothelial cell interactions, summarize the signaling pathways that have been identified to be involved in pericyte detachment from the vascular wall, and present pathological endothelial responses in the context of disease of the kidney.

Fig. 1

a, b Immunofluorescent micrograph of an uninjured kidney section in a collagen 1a1gfp transgenic mouse. In the interstitium of the kidney, peritubulary capillaries (CD31-cy3 staining) are in close apposition to coll1a1gfp-expressing cells. In most places, both cell types are separated by basal lamina (blue laminin staining) marked by arrows (a), while in some places no separation can be found (arrows in b). Note that long coll1a1gfp-positive processes can be found throughout the pericapillary compartment (scale bars = 10 µm). c Schematic of b representing pericyte (green)-endothelial cell (red) interaction; blue represents the CBM. Peg-and-socket junctions can be found in places where no separation via the CBM occurs.

Fig. 2

Schematic of pericyte detachment upon a disease stimulus followed by microvascular rarefaction and the occurrence of myofibroblasts and extracellular matrix within the interstitium, representing fibrosis.

Fig. 3

Schematic illustration of the pathways identified to be involved in pericyte detachment and vascular rarefaction at the pericyte-endothelial interface. ADAMTS-1/TIMP3 signaling [22], PDGF-B VEGF-A signaling [71], WNT signaling [88], ephrinB2 signaling [23], and ANGPT1/ANGPT2 signaling [93].