Molecular Mechanisms of Cerebrovascular Diseases

Andjelkovic, Anuska V.; Keep, Richard F.; Wang, Michael M.

doi:10.3390/ijms23137161

Cited by 4 publications

(2 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Brain vascular abnormalities can lead to various, sometimes life-threatening forms of cerebrovascular disease 6 , including ischemic and hemorrhagic stroke, vascular malformations, vascular cognitive impairment, and dementia. Within this category, cerebral small vessel diseases (CSVDs) encompass a range of sporadic or hereditary pathological alterations of cerebral arterioles, capillaries, and venules, occurring primarily within the white matter.…”

Section: Introductionmentioning

confidence: 99%

Endolysosomal dysfunction in radial glia progenitor cells leads to defective cerebral angiogenesis and compromised Blood-Brain Barrier integrity

Bassi,

Grunspan,

Hen

et al. 2023

Preprint

View full text Add to dashboard Cite

The neurovascular unit (NVU) is a complex structure comprising neurons, glia, and pericytes that interact with specialized endothelial cells to maintain cerebral homeostasis and blood-brain barrier (BBB) integrity. Alterations to NVU formation and function can lead to serious forms of cerebrovascular disease, including cerebral small vessel diseases (CSVDs), a range of pathological changes of cerebral capillaries within the white matter contributing to BBB dysfunction and demyelination. Despite the growing recognition of the pivotal roles played by neuro-vascular and glia-vascular interfaces in NVU formation and functioning, CSVD research has mainly focused on characterizing pericyte and EC dysfunction, leaving our understanding of the contribution of non-vascular cells of the brain parenchyma limited. Here, we use a novel zebrafish mutant to delve into the intricate interplay among NVU components and demonstrate how the compromised specification of a progenitor cell population sets off a cascade of events, ultimately leading to severe cerebrovascular abnormalities. The mutation affects Scavenger Receptor B2 (scarb2)/Lysosomal Membrane Protein 2 (limp2), a highly conserved protein residing in the membrane of late endosomes and lysosomes. We find Scarb2 to be predominantly expressed in Radial Glia Cells (RGCs), a multipotent cell giving rise to neurons and glia in both zebrafish and mammals. Through live imaging and genetic manipulations, we identify impaired Notch3 signaling in RGCs and their glial progeny as the primary consequence of Scarb2a depletion and show that this disruption causes excessive neurogenesis at the expense of glial cell differentiation. We further pinpoint compromised acidification of the endolysosomal compartment in mutant cells as the underlying cause of disrupted Notch3 processing, linking for the first time Notch3 defects in non-vascular cells of the brain parenchyma to CSVD phenotypes. Given the evolutionary conservation of SCARB2 expression and the remarkable recapitulation of CSVD phenotypes, scarb2 mutants provide a promising framework for investigating the mechanisms governing Notch3 processing in non-vascular cells and their involvement in the onset of CSVD.

show abstract

Section: Introductionmentioning

confidence: 99%

Endolysosomal dysfunction in radial glia progenitor cells leads to defective cerebral angiogenesis and compromised Blood-Brain Barrier integrity

Bassi,

Grunspan,

Hen

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Cardiovascular and cerebrovascular diseases remain the primary cause of death all over the world and are accompanied with severe complications ( 1 , 2 ). As a pathological basis of cardiovascular and cerebrovascular diseases, atherosclerosis (AS) is viewed as a chronic and progressive disease of the arterial wall ( 3 ).…”

Section: Introductionmentioning

confidence: 99%

Sarsasapogenin blocks ox-LDL-stimulated vascular smooth muscle cell proliferation, migration, and invasion through suppressing STIM1 expression

Zhai¹,

Liu²,

Shang³

et al. 2023

Cardiovasc Diagn Ther

View full text Add to dashboard Cite

Background Atherosclerosis (AS) is a pathological vascular disorder responsible for the majority of cardiovascular deaths. Sarsasapogenin (Sar) is a natural steroidal compound which has been extensively applied to multiple human diseases due to its pharmacological properties. In the present paper, the impacts of Sar on oxidized low-density lipoprotein (ox-LDL)-treated vascular smooth muscle cells (VSMCs) and its possible action mechanism were investigated. Methods Firstly, Cell Counting Kit-8 (CCK-8) estimated the viability of VSMCs following treatment with ascending doses of Sar. Then, VSMCs were treated by ox-LDL to stimulate an in vitro cell model of AS. CCK-8 and 5-Ethynyl-2’-deoxyuridine (EDU) assays were used to assess cell proliferation. Wound healing and transwell assays were applied to measure the migratory and invasive capacities, respectively. The expression of proliferation-, metastasis-, and stromal interaction molecule 1 (STIM1)/Orai signaling-associated proteins was measured by western blot. Results The experimental data illuminated that Sar treatment noticeably protected against ox-LDL-elicited VSMCs proliferation, migration, and invasion. Besides, Sar lowered the elevated STIM1 and Orai expression in ox-LDL-treated VSMCs. Further, STIM1 elevation partially abrogated the impacts of Sar on the proliferation, migration, and invasion of VSMCs challenged with ox-LDL. Conclusions In conclusion, Sar might reduce STIM1 expression to impede the aggressive phenotypes of ox-LDL-treated VSMCs.

show abstract

Endolysosomal dysfunction in radial glia progenitor cells leads to defective cerebral angiogenesis and compromised blood-brain barrier integrity

Bassi,

Grunspan,

Hen

et al. 2024

Nat Commun

View full text Add to dashboard Cite

Molecular Mechanisms of Cerebrovascular Diseases

Abstract: Cerebrovascular disease involves a range of conditions including ischemic and hemorrhagic stroke, vascular malformations, and vascular cognitive impairment and dementia (VCID) [...]

Cited by 4 publications

References 16 publications

Endolysosomal dysfunction in radial glia progenitor cells leads to defective cerebral angiogenesis and compromised Blood-Brain Barrier integrity

Endolysosomal dysfunction in radial glia progenitor cells leads to defective cerebral angiogenesis and compromised Blood-Brain Barrier integrity

Sarsasapogenin blocks ox-LDL-stimulated vascular smooth muscle cell proliferation, migration, and invasion through suppressing STIM1 expression

Endolysosomal dysfunction in radial glia progenitor cells leads to defective cerebral angiogenesis and compromised blood-brain barrier integrity

Contact Info

Product

Resources

About