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Adult-induced genet...
Adult-induced genetic ablation distinguishes PDGFB roles in blood-brain barrier maintenance and development
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- Vazquez-Liebanas, Elisa (author)
- Uppsala universitet,Vaskulärbiologi
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- Nahar, Khayrun (author)
- Uppsala universitet,Vaskulärbiologi
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- Bertuzzi, Giacomo (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Keller, Annika (author)
- Zurich Univ, Zurich Univ Hosp, Clin Neuroctr, Dept Neurosurg, Zurich, Switzerland.
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- Betsholtz, Christer (author)
- Uppsala universitet,Vaskulärbiologi,Karolinska Inst, Dept Med Huddinge, Campus Flemingsberg, Huddinge, Sweden
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- Andaloussi Mäe, Maarja (author)
- Uppsala universitet,Vaskulärbiologi
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(creator_code:org_t)
- SAGE Publications, 2022
- 2022
- English.
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In: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 42:2, s. 264-279
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Abstract
Subject headings
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- 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 ≈50% decrease in endothelial:pericyte cell ratio, ≈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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- Adult brain vasculature
- blood-brain barrier
- blood-retina barrier
- PDGFB
- pericyte
- platelet-derived growth factor
- vascular smooth muscle cell
- permeability
Publication and Content Type
- ref (subject category)
- art (subject category)
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