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Investigating von Willebrand Factor Pathophysiology Using a Flow Chamber Model of von Willebrand Factor-platelet String Formation
Published on: August 14, 2017
Cadmium, von Willebrand factor and vascular aging
Xia Wang1, Maria N Starodubtseva2,3, Carolyn M Kapron4
1Institute of Microvascular Medicine, The First Affiliated Hospital of Shandong First Medical University& Shandong Provincial Qianfoshan Hospital, Jinan, China.
Insights
Vascular aging, driven by endothelial dysfunction, is worsened by elevated von Willebrand Factor (vWF). Low-dose cadmium exposure increases vWF, posing a risk for cardiovascular disease and vascular aging.
Area of Science:
- Cardiovascular Science
- Environmental Health
- Molecular Biology
Background:
- Vascular aging contributes significantly to cardiovascular disease, characterized by thickened and stiffened blood vessels.
- Endothelial cell dysfunction, driven by oxidative stress and inflammation, underlies vascular aging.
- Elevated plasma levels of von Willebrand Factor (vWF), a glycoprotein involved in coagulation, are associated with aging and promote thrombosis and atherosclerosis.
Purpose of the Study:
- To review the molecular mechanisms linking vWF to vascular aging pathologies.
- To examine how cadmium (Cd) exposure influences vWF expression.
- To propose low-dose Cd as a risk factor for vascular aging via vWF elevation.
Main Methods:
- Literature review of molecular mechanisms.
- Analysis of studies on vWF in vascular aging.
- Examination of research on cadmium's effects on endothelial cells and vWF.
Main Results:
- Elevated vWF exacerbates vascular aging by promoting thrombosis, plaque formation, and smooth muscle cell proliferation.
- Low-dose cadmium exposure, while activating pro-survival pathways, enhances intima-media thickness and atherogenesis.
- Cadmium exposure increases endothelial vWF expression and secretion both in vivo and in vitro.
Conclusions:
- vWF plays a critical role in the pathologies associated with vascular aging.
- Cadmium exposure at low doses elevates vWF levels.
- Low-dose cadmium exposure is a potential risk factor for vascular aging, mediated by increased plasma vWF.
Abstract:
Vascular aging is a major contributing factor to cardiovascular disease. The aged blood vessels, characterized by vascular wall thickening and stiffening, are instigated by endothelial cell dysfunction induced by oxidative stress and inflammation. von Willebrand Factor (vWF) is a glycoprotein known for its role in coagulation, and plasma levels of vWF are increased with age. Elevated vWF promotes thrombosis, atherosclerotic plaque formation, inflammation and proliferation of vascular smooth muscle cells. Cadmium (Cd) is an environmental pollutant associated with increased morbidity and mortality of cardiovascular disease. At low concentrations, Cd activates pro-survival signaling in endothelial cells, however enhances intima-media thickness and atherogenesis. A non-cytotoxic dose of Cd also increases endothelial vWF expression and secretion in vivo and in vitro. In this review, we summarize the molecular mechanisms underlying vWF-promoted vascular aging-associated pathologies and Cd-induced vWF expression. In addition, we propose that exposure to low-dose Cd is a risk factor for vascular aging, through elevation of plasma vWF.
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