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The impact of manganese on vascular endothelium
Gustavo H Oliveira-Paula1, Airton C Martins1, Beatriz Ferrer1
1Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461 USA.
Abstract:
Manganese (Mn) is an essential trace element involved in various physiological processes, but excessive exposure may lead to toxicity. The vascular endothelium, a monolayer of endothelial cells within blood vessels, is a primary target of Mn toxicity. This review provides a comprehensive overview of the impact of Mn on vascular endothelium, focusing on both peripheral and brain endothelial cells. In vitro studies have demonstrated that high concentrations of Mn can induce endothelial cell cytotoxicity, increase permeability, and disrupt cell-cell junctions through mechanisms involving oxidative stress, mitochondrial damage, and activation of signaling pathways, such as Smad2/3-Snail. Conversely, low concentrations of Mn may protect endothelial cells from the deleterious effects of high glucose and advanced glycation end-products. In the central nervous system, Mn can cross the blood-brain barrier (BBB) and accumulate in the brain parenchyma, leading to neurotoxicity. Several transport mechanisms, including ZIP8, ZIP14, and SPCA1, have been identified for Mn uptake by brain endothelial cells. Mn exposure can impair BBB integrity by disrupting tight junctions and increasing permeability. In vivo studies have corroborated these findings, highlighting the importance of endothelial barriers in mediating Mn toxicity in the brain and kidneys. Maintaining optimal Mn homeostasis is crucial for preserving endothelial function, and further research is needed to develop targeted therapeutic strategies to prevent or mitigate the adverse effects of Mn overexposure.
Insights
Manganese (Mn) toxicity harms vascular endothelium, affecting the blood-brain barrier and leading to neurotoxicity. Maintaining optimal Mn levels is crucial for endothelial health and preventing adverse effects.
Area of Science:
- Environmental Health
- Toxicology
- Cell Biology
Background:
- Manganese (Mn) is an essential trace element with critical physiological roles.
- Excessive manganese exposure can lead to significant toxicity, particularly affecting the vascular endothelium.
- The vascular endothelium, lining blood vessels, is a key target for manganese-induced damage.
Purpose of the Study:
- To review the multifaceted impact of manganese on vascular endothelial cells, both in peripheral circulation and the central nervous system.
- To elucidate the mechanisms underlying manganese toxicity in endothelial cells.
- To explore the role of endothelial barriers in mediating manganese toxicity.
Main Methods:
- Review of in vitro studies on endothelial cell responses to varying manganese concentrations.
- Analysis of in vivo studies investigating manganese effects on brain and kidney endothelial barriers.
- Examination of identified manganese transport mechanisms in brain endothelial cells.
Main Results:
- High manganese concentrations induce endothelial cell cytotoxicity, increased permeability, and disrupted cell junctions via oxidative stress and signaling pathways.
- Low manganese concentrations may offer protective effects against high glucose and advanced glycation end-products.
- Manganese impairs blood-brain barrier integrity and contributes to neurotoxicity and kidney toxicity.
Conclusions:
- Optimal manganese homeostasis is vital for maintaining endothelial function and barrier integrity.
- Manganese toxicity poses a significant risk to vascular endothelium, impacting neurological and renal health.
- Further research is necessary to develop therapeutic strategies against manganese overexposure effects.
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