4.6 Article

Altered hemodynamics and vascular reactivity in a mouse model with severe pericyte deficiency

Journal

JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
Volume 43, Issue 5, Pages 763-777

Publisher

SAGE PUBLICATIONS INC
DOI: 10.1177/0271678X221147366

Keywords

Pericytes; brain vasculature; hemodynamics; blood oxygen; vascular reactivity

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This study found that deleting the PDGFB retention motif results in severe pericyte deficiency in the vascular network, leading to reduced cerebral vasodilation capacity and impaired oxygen delivery to the tissue. Pdgfb(ret/ret) mice also showed abnormal blood oxygen extraction, indicating a state of hypoxia. These findings suggest that severe pericyte deficiency can cause vascular abnormalities and altered cerebral blood flow, resembling arteriovenous malformations.
Pericytes are the mural cells of the microvascular network that are in close contact with underlying endothelial cells. Endothelial-secreted PDGFB leads to recruitment of pericytes to the vessel wall, but this is disrupted in Pdgfb(ret/ret) mice when the PDGFB retention motif is deleted. This results in severely reduced pericyte coverage on blood vessels. In this study, we investigated vascular abnormalities and hemodynamics in Pdgfb(ret/ret) mice throughout the cerebrovascular network and in different cortical layers by in vivo two-photon microscopy. We confirmed that Pdgfb(ret/ret) mice are severely deficient in pericytes throughout the vascular network, with enlarged brain blood vessels and a reduced number of vessel branches. Red blood cell velocity, linear density, and tube hematocrit were reduced in Pdgfb(ret/ret) mice, which may impair oxygen delivery to the tissue. We also measured intravascular PO2 and found that concentrations were higher in cortical Layer 2/3 in Pdgfb(ret/ret) mice, indicative of reduced blood oxygen extraction. Finally, we found that Pdgfb(ret/ret) mice had a reduced capacity for vasodilation in response to an acetazolamide challenge during functional MRI imaging. Taken together, these results suggest that severe pericyte deficiency can lead to vascular abnormalities and altered cerebral blood flow, reminiscent of pathologies such as arteriovenous malformations.

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