Brain Endothelial Cells Play a Central Role in the Development of Enlarged Perivascular Spaces in the Metabolic Syndrome
Brain capillary endothelial cell(s) (BECs) have numerous functions, including their semipermeable interface-barrier (transfer and diffusion of solutes), trophic (metabolic homeostasis), tonic (vascular hemodynamics), and trafficking (vascular permeability, coagulation, and leukocyte extravasation) f...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-06-01
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| Series: | Medicina |
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| Online Access: | https://www.mdpi.com/1648-9144/59/6/1124 |
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| author | Melvin R. Hayden |
| author_facet | Melvin R. Hayden |
| author_sort | Melvin R. Hayden |
| collection | DOAJ |
| description | Brain capillary endothelial cell(s) (BECs) have numerous functions, including their semipermeable interface-barrier (transfer and diffusion of solutes), trophic (metabolic homeostasis), tonic (vascular hemodynamics), and trafficking (vascular permeability, coagulation, and leukocyte extravasation) functions to provide brain homeostasis. BECs also serve as the brain’s sentinel cell of the innate immune system and are capable of antigen presentation. In metabolic syndrome (MetS), there are two regions resulting in the proinflammatory signaling of BECs, namely visceral adipose tissue depots supplying excessive peripheral cytokines/chemokines (<b><i>p</i></b>CCs) and gut microbiota dysbiotic regions supplying excessive soluble lipopolysaccharide (sLPS), small LPS-enriched extracellular vesicle exosomes (lpsEVexos), and <b><i>p</i></b>CCs. This dual signaling of BECs at their receptor sites results in BEC activation and dysfunction (BEC<i>act/dys</i>) and neuroinflammation. sLPS and lpsEVexos signal BECs’ toll-like receptor 4, which then signals translocated nuclear factor kappa B (NFkB). Translocated NFkB promotes the synthesis and secretion of BEC proinflammatory cytokines and chemokines. Specifically, the chemokine CCL5 (RANTES) is capable of attracting microglia cells to BECs. BEC neuroinflammation activates perivascular space(s) (PVS) resident macrophages. Excessive phagocytosis by reactive resident PVS macrophages results in a stagnation-like obstruction, which along with increased capillary permeability due to BEC<i>act/dys</i> could expand the fluid volume within the PVS to result in enlarged PVS (EPVS). Importantly, this remodeling may result in pre- and post-capillary EPVS that would contribute to their identification on T2-weighted MRI, which are considered to be biomarkers for cerebral small vessel disease. |
| first_indexed | 2024-03-11T02:11:21Z |
| format | Article |
| id | doaj.art-6cef22d4c5714979acf7581826b09172 |
| institution | Directory Open Access Journal |
| issn | 1010-660X 1648-9144 |
| language | English |
| last_indexed | 2024-03-11T02:11:21Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Medicina |
| spelling | doaj.art-6cef22d4c5714979acf7581826b091722023-11-18T11:31:49ZengMDPI AGMedicina1010-660X1648-91442023-06-01596112410.3390/medicina59061124Brain Endothelial Cells Play a Central Role in the Development of Enlarged Perivascular Spaces in the Metabolic SyndromeMelvin R. Hayden0Department of Internal Medicine, Endocrinology Diabetes and Metabolism, Diabetes and Cardiovascular Disease Center, University of Missouri School of Medicine, One Hospital Drive, Columbia, MO 65211, USABrain capillary endothelial cell(s) (BECs) have numerous functions, including their semipermeable interface-barrier (transfer and diffusion of solutes), trophic (metabolic homeostasis), tonic (vascular hemodynamics), and trafficking (vascular permeability, coagulation, and leukocyte extravasation) functions to provide brain homeostasis. BECs also serve as the brain’s sentinel cell of the innate immune system and are capable of antigen presentation. In metabolic syndrome (MetS), there are two regions resulting in the proinflammatory signaling of BECs, namely visceral adipose tissue depots supplying excessive peripheral cytokines/chemokines (<b><i>p</i></b>CCs) and gut microbiota dysbiotic regions supplying excessive soluble lipopolysaccharide (sLPS), small LPS-enriched extracellular vesicle exosomes (lpsEVexos), and <b><i>p</i></b>CCs. This dual signaling of BECs at their receptor sites results in BEC activation and dysfunction (BEC<i>act/dys</i>) and neuroinflammation. sLPS and lpsEVexos signal BECs’ toll-like receptor 4, which then signals translocated nuclear factor kappa B (NFkB). Translocated NFkB promotes the synthesis and secretion of BEC proinflammatory cytokines and chemokines. Specifically, the chemokine CCL5 (RANTES) is capable of attracting microglia cells to BECs. BEC neuroinflammation activates perivascular space(s) (PVS) resident macrophages. Excessive phagocytosis by reactive resident PVS macrophages results in a stagnation-like obstruction, which along with increased capillary permeability due to BEC<i>act/dys</i> could expand the fluid volume within the PVS to result in enlarged PVS (EPVS). Importantly, this remodeling may result in pre- and post-capillary EPVS that would contribute to their identification on T2-weighted MRI, which are considered to be biomarkers for cerebral small vessel disease.https://www.mdpi.com/1648-9144/59/6/1124brain capillary endothelial cell(s) |
| spellingShingle | Melvin R. Hayden Brain Endothelial Cells Play a Central Role in the Development of Enlarged Perivascular Spaces in the Metabolic Syndrome Medicina brain capillary endothelial cell(s) |
| title | Brain Endothelial Cells Play a Central Role in the Development of Enlarged Perivascular Spaces in the Metabolic Syndrome |
| title_full | Brain Endothelial Cells Play a Central Role in the Development of Enlarged Perivascular Spaces in the Metabolic Syndrome |
| title_fullStr | Brain Endothelial Cells Play a Central Role in the Development of Enlarged Perivascular Spaces in the Metabolic Syndrome |
| title_full_unstemmed | Brain Endothelial Cells Play a Central Role in the Development of Enlarged Perivascular Spaces in the Metabolic Syndrome |
| title_short | Brain Endothelial Cells Play a Central Role in the Development of Enlarged Perivascular Spaces in the Metabolic Syndrome |
| title_sort | brain endothelial cells play a central role in the development of enlarged perivascular spaces in the metabolic syndrome |
| topic | brain capillary endothelial cell(s) |
| url | https://www.mdpi.com/1648-9144/59/6/1124 |
| work_keys_str_mv | AT melvinrhayden brainendothelialcellsplayacentralroleinthedevelopmentofenlargedperivascularspacesinthemetabolicsyndrome |