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Dynamic regulator of the blood-brain barrier
By Maarja Andaloussi Mäe
24 February, 2021
Confocal microscope image of a lonely pericyte (orange) trying to cover as much of the blood vessels (gray) as possible in a pericyte-deficient adult mouse brain.
Pericytes and vascular smooth muscle cells, collectively referred to as vascular mural cells, form together with the endothelial cells the cellular component of the blood vessel wall. While vascular smooth muscle cells surround arteries and veins and regulate vascular tone and diameter, pericytes are typically surrounding the blood capillaries. Pericyte morphology, distribution and density vary between organs and vascular beds. The central nervous system capillaries have a high pericyte density compared to peripheral organs, suggesting a specific importance of pericytes in the brain. Indeed, studies suggest that pericytes are critically required for the establishment of fully functional blood-brain and blood-retina barriers. Developmental absence or reduction of pericytes leads to increased endothelial leakage of molecules from the blood into the brain, misexpression of molecular transporters and leukocyte adhesion molecules.
A number of central nervous system conditions have been associated with pericyte loss or damage, including diabetic retinopathy, stroke, Alzheimer’s disease, amyotrophic lateral sclerosis and aging. However, whether pericyte loss or damage contributes causally to these conditions, and how and to what extent pericytes regulate the functional state of vasculature are still not clear.
Our studies on adult pericyte-deficient mice have revealed that brain endothelial cells without pericyte contact retain a general blood-brain barrier-specific gene expression profile, acquire a skewed arterio-venous zonation, start expressing numerous growth factors and regulatory proteins that are usually not expressed in the adult brain, show angiogenic sprouting and display two modes of blood-brain barrier permeability- increased transcytosis and focal hot-spot leakage sites. One of the upregulated growth factors, ANGPT2, in pericyte-deficient endothelium exerts protective rather than destabilizing function, however it remains to be determined if ANGPT2 acts as an agonist via TIE2 receptor specifically in a blood-brain barrier microenvironment.
Our data show that the endothelial response to pericyte loss is complex, which could be also expected in diseases mentioned above.
About the author:
Maarja is a researcher in Christer Betsholtz laboratory. She studies the role of pericytes in the brain endothelium. She is analyzing the adult viable pericyte-deficient mouse brain vasculature using reverse genetics, exogenous fluorescent tracers, single-cell RNA sequencing and immunofluorescent stainings.
Maarja Andaloussi Mäe, PhD
Dept. Immunology, Genetics and Pathology
Rudbeck Laboratory C11
Dag Hammarskjölds Väg 20
751 85 Uppsala