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Antioxidants, von Willebrand factor and endothelial cell injury in hypercholesterolaemia and vascular disease
A D Blann1, S R Maxwell, G Burrows
1Department of Surgery, University Hospital of South Manchester, Didsbury, UK.
Insights
Patients with hypercholesterolaemia exhibit reduced antioxidant capacity, particularly those with vascular disease. This impaired antioxidant defense, indicated by lower glutathione peroxidase and higher von Willebrand factor, suggests increased oxidative stress contributes to atherosclerosis.
Area of Science:
- Cardiovascular Research
- Oxidative Stress Biology
- Clinical Biochemistry
Background:
- Hyperlipidaemia is a significant risk factor for cardiovascular disease.
- Endothelial dysfunction plays a crucial role in the pathogenesis of atherosclerosis.
- Oxidative stress, arising from an imbalance between free radicals and antioxidants, is implicated in endothelial injury.
Purpose of the Study:
- To investigate the relationship between antioxidant status and endothelial cell injury in patients with hyperlipidaemia.
- To compare antioxidant capacity and markers of endothelial injury in hyperlipidaemic patients with and without vascular disease.
- To explore the association between serum antioxidant levels, endothelial markers, and the presence of vascular disease.
Main Methods:
- Serum levels of total antioxidant capacity, glutathione peroxidase, and von Willebrand factor (vWf) were measured.
- Lipid profiles and vWf were assessed in 119 hyperlipidaemic patients and 58 healthy controls.
- Patients were stratified based on the presence or absence of clinically apparent vascular disease.
Main Results:
- Hyperlipidaemic patients showed significantly lower total antioxidant capacity and glutathione peroxidase compared to controls.
- Patients with vascular disease had lower glutathione peroxidase and higher vWf levels than those without vascular disease.
- vWf was inversely correlated with glutathione peroxidase, suggesting a link between reduced antioxidant defense and endothelial activation.
Conclusions:
- Patients with hypercholesterolaemia possess diminished antioxidant capacity, which is more pronounced in those with established vascular disease.
- Elevated vWf in hypercholesterolaemia, especially with vascular disease, indicates endothelial injury potentially driven by oxidative stress.
- These findings suggest that reduced antioxidant defense in hypercholesterolaemia contributes to endothelial dysfunction and the development of atherosclerosis.
Abstract:
The relationship between antioxidants and endothelial cell injury was examined in 119 patients with (n = 48) or without (n = 71) vascular disease who were attending a hyperlipidaemia clinic. Serum levels of total antioxidant capacity, glutathione peroxidase (a protein antioxidant), von Willebrand factor (vWf, a specific endothelial cell product and marker of injury) and routine lipids were measured in the patients and from 58 healthy controls. Compared to controls, total antioxidant capacity (P < 0.01) and glutathione peroxidase (P < 0.0001) were lower whilst vWf was higher (P < 0.0001) amongst the patients. Comparing patients with and without vascular disease, glutathione peroxidase was lower (P < 0.03) and vWf was higher (P < 0.05) in the presence of vascular disease but there was no difference in levels of serum lipids or total antioxidant capacity. vWf and glutathione peroxidase were inversely correlated (r = -0.26, P < 0.005). We conclude that patients with hypercholesterolaemia have reduced antioxidant capacity and this is most severe in patients with clinically apparent vascular disease. This, linked to the finding of increased vWf in hypercholesterolaemia with highest levels in those patients with vascular disease, suggests that loss of antioxidant capacity may expose the vascular endothelium to excess oxidative damage. These results suggest a link between hypercholesterolaemia, impaired ability to resist free radical attack, and the development of atherosclerosis.