Roles of endothelial dysfunction and injury in mercury-induced cardiotoxicity
- UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
- Joshua Fowler (Creator)
- Institution
- The University of North Carolina at Greensboro (UNCG )
- Web Site: http://library.uncg.edu/
- Advisor
- Zhenquan Jia
Abstract: Cardiovascular disease (CVD) is the leading global cause of mortality and morbidity and presents a significant economic impact in the form of healthcare costs. The development of cardiovascular disease has many facets ranging from unhealthy lifestyle choices to unavoidable environmental toxins. Among these toxins that contribute to CVD, environmental and dietary exposure to organic mercury, in the form of methyl mercury (MeHg), presents a considerable cause for concern. Human exposure to this toxin has increased as a surge of industrialization sweeps the globe and many people are unaware that their normal diet, especially intake of fish and rice, has exposed them to MeHg. While traditionally labeled a neurotoxin, MeHg has been epidemiologically linked to CVD pathologies; However, its role in development and promotion of atherosclerosis, an initial step in more immediately life-threatening CVDs, remains unclear. Human microvascular endothelial cells (HMEC-1) are a well-characterized endothelial cell line that retains many important biomarkers and properties of human vascular cells. This study was conducted to examine the role that MeHg plays in the adhesion of circulating monocytes to vascular endothelial cells, a critical step in atherosclerosis, and attempts to clarify the underlying mechanisms. MeHg treatment significantly induced the adhesion of monocyte to HMEC-1 endothelial cells, while also upregulating the production of proinflammatory cytokines interleukin-6 (IL-6), interleukin-8 (IL-8). Further, MeHg treatment also upregulated the chemotactic cytokine monocyte chemoattractant protein-1 and intercellular adhesion molecule-1 (ICAM-1). These molecules are imperative for the firm adhesion of leukocytes to endothelial cells. Additionally, the nuclear factor kappa B (NF-?B) signaling pathway is an important regulator in the expression of adhesion molecules and chemokines. Our results further demonstrated that MeHg stimulated a significant increase in NF-?B activation as measured by the eLUCIdate™ NF-?B reporter cell line. These findings suggest that NF-?B signaling pathway activation by MeHg is an important factor in the binding of monocytes to endothelial cells. Finally, cell death by necrosis has been suggested to contribute to endothelial cell dysfunction promoting cytokine release into the surrounding cellular matrix, exacerbating atherosclerotic development [1]. By using flow cytometric analysis with 7-AAD and AnnexinV/PI, MeHg treatment only caused a significant increase in necrotic cell death at 2.0 µM concentrations without initiating apoptosis. This study provides new insights into the molecular actions of MeHg that can lead to endothelial dysfunction, inflammation and subsequent atherosclerotic development. This contributes to our understanding of the detrimental effects of human exposure to MeHg which remains an important human health concern in a rapidly industrializing world. [This abstract has been edited to remove characters that will not display in this system. Please see the PDF for the full abstract.]
Roles of endothelial dysfunction and injury in mercury-induced cardiotoxicity
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Created on 8/1/2019
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Additional Information
- Publication
- Thesis
- Language: English
- Date: 2019
- Keywords
- Atherosclerosis, Cardiovascular, Methyl mercury
- Subjects
- Methylmercury $x Physiological effect
- Methylmercury $x Toxicology
- Vascular endothelial cells
- Atherosclerosis $x Etiology
- Cardiovascular system $x Pathophysiology