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Published on: October 12, 2017
Low-density lipoprotein cholesterol determines oxidative stress and endothelial dysfunction in saphenous veins from
Sammy Al-Benna1, Carlene A Hamilton, John D McClure
1BHF Glasgow Cardiovascular Research Centre, Division of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.
Insights
Oxidative stress and superoxide levels are elevated in coronary artery disease (CAD) patients, contributing to endothelial dysfunction. Lowering low-density lipoprotein (LDL) cholesterol is crucial for managing this condition.
Area of Science:
- Cardiovascular Science
- Oxidative Stress Research
- Endothelial Function Studies
Background:
- Endothelial dysfunction is linked to cardiovascular disease.
- The specific role of oxidative stress in this relationship requires further elucidation.
Purpose of the Study:
- To investigate the role of oxidative stress in endothelial dysfunction in patients with severe coronary artery disease (CAD).
- To determine the impact of low-density lipoprotein (LDL) cholesterol on endothelial function and oxidative stress markers in CAD patients.
Main Methods:
- Studied 188 severe CAD patients and 51 healthy controls.
- Assessed saphenous vein relaxation, vascular superoxide levels, and oxidative stress markers.
- Utilized calcium ionophore, apocynin, and allopurinol for relaxation studies.
Main Results:
- CAD patients exhibited significantly decreased saphenous vein relaxation compared to controls (26% vs 60%).
- Vascular superoxide production was markedly increased in CAD patients (0.89 vs 0.56 nmol/mg per min).
- Apocynin and allopurinol showed a greater effect on vasorelaxation in CAD patients, indicating increased oxidative stress.
Conclusions:
- Endothelial dysfunction in CAD is associated with elevated superoxide and oxidative stress biomarkers in saphenous veins.
- LDL cholesterol is a primary determinant of endothelial dysfunction and oxidative stress in these patients.
- Findings support aggressive LDL cholesterol-lowering therapies for CAD management.
Objective:
There is evidence for a relationship between endothelial dysfunction and cardiovascular disease, but a causative role for oxidative stress remains to be determined.
Methods And Results:
We studied 188 patients with severe coronary artery disease (CAD), of whom 51 were age and sex matched with 51 healthy controls undergoing varicose vein surgery. Relaxation of saphenous vein to calcium ionophore, apocynin, and allopurinol was studied together with the markers of oxidative stress, total antioxidant capacity and reduced/oxidized glutathione ratio. Vascular superoxide levels were measured using lucigenin chemiluminescence and hydroethidine. Relaxation to calcium ionophore was decreased in CAD compared with control patients (maximum relaxation 26+/-2% versus 60+/-1%; P<0.001). Total superoxide production was increased (0.89+/-0.09 versus 0.56+/-0.06 nmol/mg per min; P=0.008), whereas superoxide inhibition with apocynin or allopurinol had a greater effect on vasorelaxation in CAD patients. Low-density lipoprotein (LDL) cholesterol predicted relaxation to calcium ionophore (P<0.001) and oxidative stress markers (P<0.001) in CAD patients.
Conclusions:
Endothelial dysfunction is associated with raised levels of superoxide and biomarkers of oxidative stress in saphenous veins from CAD patients. LDL cholesterol is a major determinant of endothelial dysfunction and oxidative stress in these patients. These results support intensive LDL cholesterol-lowering therapy as suggested by recent clinical trials.
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