Cadmium exposure enhances VE‑cadherin expression in endothelial cells via suppression of ROCK signaling

Li, Xiaorui; Li, Xiao; Sun, Rong; Gao, Mei Hua; Wang, Hui

doi:10.3892/etm.2022.11282

Cited by 3 publications

(2 citation statements)

References 42 publications

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“…In contrast, the application of ROCK inhibitor SR3677 mitigated the fragmentation of VE-cadherin caused by LEI-106. This data aligns well with former work published by Li et al [ 40 ]. Their results showed that ROCK pathway inhibitor Y27632 increased VE-cadherin expression in human umbilical vein endothelial cells.…”

Section: Discussionsupporting

confidence: 94%

Depletion of Endothelial-Derived 2-AG Reduces Blood-Endothelial Barrier Integrity via Alteration of VE-Cadherin and the Phospho-Proteome

Levine,

Liktor-Busa,

Balasubramanian

et al. 2023

IJMS

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Mounting evidence supports the role of the endocannabinoid system in neurophysiology, including blood–brain barrier (BBB) function. Recent work has demonstrated that activation of endocannabinoid receptors can mitigate insults to the BBB during neurological disorders like traumatic brain injury, cortical spreading depression, and stroke. As alterations to the BBB are associated with worsening clinical outcomes in these conditions, studies herein sought to examine the impact of endocannabinoid depletion on BBB integrity. Barrier integrity was investigated in vitro via bEnd.3 cell monolayers to assess endocannabinoid synthesis, barrier function, calcium influx, junctional protein expression, and proteome-wide changes. Inhibition of 2-AG synthesis using DAGLα inhibition and siRNA inhibition of DAGLα led to loss of barrier integrity via altered expression of VE-cadherin, which could be partially rescued by exogenous application of 2-AG. Moreover, the deleterious effects of DAGLα inhibition on BBB integrity showed both calcium and PKC (protein kinase C)-dependency. These data indicate that disruption of 2-AG homeostasis in brain endothelial cells, in the absence of insult, is sufficient to disrupt BBB integrity thus supporting the role of the endocannabinoid system in neurovascular disorders.

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Section: Discussionsupporting

confidence: 94%

Depletion of Endothelial-Derived 2-AG Reduces Blood-Endothelial Barrier Integrity via Alteration of VE-Cadherin and the Phospho-Proteome

Levine,

Liktor-Busa,

Balasubramanian

et al. 2023

IJMS

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show abstract

“…Along with induction of proapoptotic signaling, Cd exposure also up-regulated mRNA expression of adhesion molecules ICAM-1 and VCAM-1, as well as VE-cadherin [ 100 , 101 ]. Cd-induced up-regulation of von Willebrand factor mRNA and protein expression though stimulation of ETS-related gene (ERG) transcription factor signaling, but not NF-κB and GATA3 signaling, may also contribute to atherogenesis.…”

Section: Introductionmentioning

confidence: 99%

Association between Heavy Metals, Metalloids and Metabolic Syndrome: New Insights and Approaches

Martins

Ferrer

Tinkov

et al. 2023

Toxics

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Metabolic syndrome (MetS) is an important public health issue that affects millions of people around the world and is growing to pandemic-like proportions. This syndrome is defined by the World Health Organization (WHO) as a pathologic condition characterized by abdominal obesity, insulin resistance, hypertension, and hyperlipidemia. Moreover, the etiology of MetS is multifactorial, involving many environmental factors, including toxicant exposures. Several studies have associated MetS with heavy metals exposure, which is the focus of this review. Environmental and/or occupational exposure to heavy metals are a major risk, contributing to the development of chronic diseases. Of particular note, toxic metals such as mercury, lead, and cadmium may contribute to the development of MetS by altering oxidative stress, IL-6 signaling, apoptosis, altered lipoprotein metabolism, fluid shear stress and atherosclerosis, and other mechanisms. In this review, we discuss the known and potential roles of heavy metals in MetS etiology as well as potential targeted pathways that are associated with MetS. Furthermore, we describe how new approaches involving proteomic and transcriptome analysis, as well as bioinformatic tools, may help bring about an understanding of the involvement of heavy metals and metalloids in MetS.

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Contraction of human brain vascular pericytes in response to islet amyloid polypeptide is reversed by pramlintide

et al. 2023

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The islet amyloid polypeptide (IAPP), a pancreas-produced peptide, has beneficial functions in its monomeric form. However, IAPP aggregates, related to type 2 diabetes mellitus (T2DM), are toxic not only for the pancreas, but also for the brain. In the latter, IAPP is often found in vessels, where it is highly toxic for pericytes, mural cells that have contractile properties and regulate capillary blood flow. In the current study, we use a microvasculature model, where human brain vascular pericytes (HBVP) are co-cultured together with human cerebral microvascular endothelial cells, to demonstrate that IAPP oligomers (oIAPP) alter the morphology and contractility of HBVP. Contraction and relaxation of HBVP was verified using the vasoconstrictor sphingosine-1-phosphate (S1P) and vasodilator Y27632, where the former increased, and the latter decreased, the number of HBVP with round morphology. Increased number of round HBVP was also seen after oIAPP stimulation, and the effect was reverted by the IAPP analogue pramlintide, Y27632, and the myosin inhibitor blebbistatin. Inhibition of the IAPP receptor with the antagonist AC187 only reverted IAPP effects partially. Finally, we demonstrate by immunostaining of human brain tissue against laminin that individuals with high amount of brain IAPP levels show significantly lower capillary diameter and altered mural cell morphology compared to individuals with low brain IAPP levels. These results indicate that HBVP, in an in vitro model of microvasculature, respond morphologically to vasoconstrictors, dilators, and myosin inhibitors. They also suggest that oIAPP induces contraction of these mural cells and that pramlintide can reverse such contraction.

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Cadmium exposure enhances VE‑cadherin expression in endothelial cells via suppression of ROCK signaling

Cited by 3 publications

References 42 publications

Depletion of Endothelial-Derived 2-AG Reduces Blood-Endothelial Barrier Integrity via Alteration of VE-Cadherin and the Phospho-Proteome

Depletion of Endothelial-Derived 2-AG Reduces Blood-Endothelial Barrier Integrity via Alteration of VE-Cadherin and the Phospho-Proteome

Association between Heavy Metals, Metalloids and Metabolic Syndrome: New Insights and Approaches

Contraction of human brain vascular pericytes in response to islet amyloid polypeptide is reversed by pramlintide

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