Pericyte dysfunction is a key mediator of the risk of cerebral ischemia

Whitehead, Bailey; Karelina, Kate; Weil, Zachary M.

doi:10.1002/jnr.25245

Cited by 5 publications

(2 citation statements)

References 122 publications

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“…This may be attributed to the different sources of PCs, indicating that PCs have tissue specificity. Previous studies have mostly focused on cerebrovascular PCs [41,42], and we concentrated on the tube-forming ability of skin PCs in this study.…”

Section: Discussionmentioning

confidence: 99%

Tube Formation Capability and Chemotaxis of Skin Pericytes

Cui,

Lin,

Zhao

et al. 2024

Discovery Medicine

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Background: Pericytes (PCs), the critical components of vessels, are implicated in wound repair. This study aimed to explore the roles of PCs in wound healing and angiogenesis. Methods: Skin PCs and human dermal microvascular endothelial cells (HDMECs) were isolated from patients' upper eyelid skin. Immunofluorescence staining was used to characterize the morphology of PCs. Tube formation and transwell chemotaxis assays were performed to explore PC's tube-forming capability and chemotaxis. Finally, we investigated the effects of PCs and endothelial cells on wound repair using skin wound of a rat model. Results: Skin PCs exhibited a double-protrusion structure and characteristic antigen expression of neural/glial antigen 2 (NG2) + /platelet-derived growth factor receptor-β (PDGFR-β) + /alpha-smooth muscle actin (α-SMA) + /CD31 − . Skin PCs could directly form lumen-like structures in a two dimensional (2D) culture environment, and mild hypoxia and starvation promoted the lumen-like structure formation. Furthermore, skin PCs quickly formed more stable lumen-like structures than HDMECs in matrigel, and they recruited HDMECs in a three dimensional (3D) culture environment. Transwell chemotaxis assay showed that PCs and HDMECs were chemotactic to each other. PCs could develop lumen-like structures in the skin wounds of rat models. The number of PCs mounted in wounded skin was compared to normal skin. The ratio of PCs to endothelial cells gradually increased after skin injury and reached its maximum on the 3rd day. Conclusions: Skin PCs have an excellent tube-forming capability and chemotaxis to endothelial cells. PCs might promote wound repair by recruiting endothelial cells.

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Section: Discussionmentioning

confidence: 99%

Tube Formation Capability and Chemotaxis of Skin Pericytes

Cui,

Lin,

Zhao

et al. 2024

Discovery Medicine

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“…They have a crucial purpose in preserving the brain’s microenvironment and facilitating various processes such as cerebral blood flow regulation, microvascular tone modulation, and maintenance of the integrity of the blood–brain barrier (BBB) [ 1 , 2 ]. Nevertheless, the impairment of the vascular endothelium is an initial clinical observation, which is strongly associated with several vascular and cerebral disorders in individuals affected by atherosclerosis, stroke, and neurodegenerative conditions [ 3 , 4 , 5 ]. The disruption and dysfunction of brain microvessels can lead to subsequent damage to neuronal cells within the surrounding microenvironment [ 3 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

Protective Effects of Sophoraflavanone G by Inhibiting TNF-α-Induced MMP-9-Mediated Events in Brain Microvascular Endothelial Cells

Lee,

Chen,

Tsai

et al. 2023

IJMS

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The regulation of matrix metalloproteinases (MMPs), especially MMP-9, has a critical role in both physiological and pathological events in the central nervous system (CNS). MMP-9 is an indicator of inflammation that triggers several CNS disorders, including neurodegeneration. Tumor necrosis factor-α (TNF-α) has the ability to stimulate the production of different inflammatory factors, including MMP-9, in several conditions. Numerous phytochemicals are hypothesized to mitigate inflammation, including the CNS. Among them, a flavonoid compound, sophoraflavanone G (SG), found in Sophora flavescens has been found to possess several medicinal properties, including anti-bacterial and anti-inflammatory effects. In this study, mouse brain microvascular endothelial cells (bMECs) were used to explore TNF-α-induced MMP-9 signaling. The effects of SG on TNF-α-induced MMP-9 expression and its mechanisms were further evaluated. Our study revealed that the expression of MMP-9 in bMECs was stimulated by TNF-α through the activation of ERK1/2, p38 MAPK, and JNK1/2 via the TNF receptor (TNFR) with a connection to the NF-κB signaling pathway. Moreover, we found that SG can interact with the TNFR. The upregulation of MMP-9 by TNF-α may lead to the disruption of zonula occludens-1 (ZO-1), which can be mitigated by SG administration. These findings provide evidence that SG may possess neuroprotective properties by inhibiting the signaling pathways associated with TNFR-mediated MMP-9 expression and the subsequent disruption of tight junctions in brain microvascular endothelial cells.

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Expression of alpha smooth muscle actin decreases with ageing and increases upon lumen obstruction in mouse brain pericytes

Győri,

Mészáros,

Krecsmarik

et al. 2024

GeroScience

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Cerebral pericytes are mural cells covering brain microvessels, organized as ensheathing, mesh and thin-strand pericytes. These latter two, together called capillary pericytes, have low levels of alpha smooth muscle actin (α-SMA), regulating basal vascular tone and applying a slow influence on cerebral blood flow. Pericytes are subject to alterations in ageing which may be even more pronounced in age-related pathologies, including microinfarcts, which usually affect a large number of vessels in the ageing brain. We modelled this condition by injecting 10 µm-size microspheres into the circulation of mice resulting in the occlusion of capillaries covered by ensheathing and mesh pericytes. We observed that α-SMA and Acta2, the gene encoding it, as well as TGF-β1/Tgfb1, the major regulator of α-SMA, decreased during ageing in cerebral microvessels. In the vicinity of the microspheres stalled in the capillaries, expression of α-SMA increased significantly in both ensheathing and especially in mesh pericytes, both in young (2 to 3 months of age) and old (24 months of age) mice. On the other hand, γ-actin was detected in endothelial cells, but not in pericytes, and decreased in microvessels of microsphere-containing hemispheres. Altogether, our data show that obstruction of cerebral microvessels increases α-SMA expression in pericytes in both age groups, but this does not compensate for the lower expression of the contractile protein in old animals. Increased α-SMA expression may lead to constriction of the obstructed vessels probably aggravating flow heterogeneity in the aged brain.

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Pericyte dysfunction is a key mediator of the risk of cerebral ischemia

Cited by 5 publications

References 122 publications

Tube Formation Capability and Chemotaxis of Skin Pericytes

Tube Formation Capability and Chemotaxis of Skin Pericytes

Protective Effects of Sophoraflavanone G by Inhibiting TNF-α-Induced MMP-9-Mediated Events in Brain Microvascular Endothelial Cells

Expression of alpha smooth muscle actin decreases with ageing and increases upon lumen obstruction in mouse brain pericytes

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