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Publication : Adult-induced genetic ablation distinguishes PDGFB roles in blood-brain barrier maintenance and development.

First Author  Vazquez-Liebanas E Year  2022
Journal  J Cereb Blood Flow Metab Volume  42
Issue  2 Pages  264-279
PubMed ID  34689641 Mgi Jnum  J:335383
Mgi Id  MGI:7432443 Doi  10.1177/0271678X211056395
Citation  Vazquez-Liebanas E, et al. (2022) Adult-induced genetic ablation distinguishes PDGFB roles in blood-brain barrier maintenance and development. J Cereb Blood Flow Metab 42(2):264-279
abstractText  Platelet-derived growth factor B (PDGFB) released from endothelial cells is indispensable for pericyte recruitment during angiogenesis in embryonic and postnatal organ growth. Constitutive genetic loss-of-function of PDGFB leads to pericyte hypoplasia and the formation of a sparse, dilated and venous-shifted brain microvasculature with dysfunctional blood-brain barrier (BBB) in mice, as well as the formation of microvascular calcification in both mice and humans. Endothelial PDGFB is also expressed in the adult quiescent microvasculature, but here its importance is unknown. We show that deletion of Pdgfb in endothelial cells in 2-months-old mice causes a slowly progressing pericyte loss leading, at 12-18 months of age, to approximately 50% decrease in endothelial:pericyte cell ratio, approximately 60% decrease in pericyte longitudinal capillary coverage and >70% decrease in pericyte marker expression. Similar to constitutive loss of Pdgfb, this correlates with increased BBB permeability. However, in contrast to the constitutive loss of Pdgfb, adult-induced loss does not lead to vessel dilation, impaired arterio-venous zonation or the formation of microvascular calcifications. We conclude that PDFGB expression in quiescent adult microvascular brain endothelium is critical for the maintenance of pericyte coverage and normal BBB function, but that microvessel dilation, rarefaction, arterio-venous skewing and calcification reflect developmental roles of PDGFB.
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