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Vascular stiffness is related to superoxide generation in the vessel wall

Delles, Christiana; Zimmerli, Lukas Ua; McGrane, David Ja; Koh-Tan, Caline HHa; Pathi, Vivek Lb; McKay, Alan Jc; Steedman, Traceya,d; Dargie, Henry Ja,d; Hamilton, Carlene Aa; Dominiczak, Anna Fa

doi: 10.1097/HJH.0b013e3282f7677c
Original papers: Oxidative stress

Objectives: Oxidative stress causes endothelial dysfunction and plays a major role in the pathogenesis of cardiovascular disease. Increased vascular stiffness is an intermediate phenotype in the development of cardiovascular disease. We hypothesized that vascular stiffness is partially determined by oxidative stress.

Methods: We examined 163 participants out of whom 80 had coronary artery disease. Vascular stiffness was assessed by pulse wave analysis, pulse wave velocity and measurement of aortic compliance by cardiac MRI. Circulating markers of oxidative stress and vascular superoxide generation in saphenous vein were measured.

Results: After adjustment for age, sex, BMI, heart rate, blood pressure and lipids only carotid-femoral pulse wave velocity and aortic compliance were different between patients and control group. Aortic compliance was reduced (11.4 ± 6.3 vs. 13.9 ± 7.3 ml × 10−3 per mmHg; P = 0.035) and vascular superoxide generation increased (1.01 ± 0.45 vs. 0.76 ± 0.44 nmol/mg per min; P = 0.035) in patients with coronary artery disease compared with those without. In a multiple stepwise regression analysis, aortic compliance was determined by age (P < 0.001) and vascular superoxide production (P = 0.033). CYBA C242T and NOS3 G894T polymorphisms had additive effects on vascular superoxide generation (P = 0.026) and xanthine oxidase activity was increased in patients with CAD (P = 0.043). Genetic factors (P = 0.033) and xanthine oxidase activity (P < 0.001) were also related to aortic compliance.

Conclusion: By measuring vascular superoxide generation and aortic compliance using cardiac MRI, we demonstrated a functional relationship between oxidative stress and vascular stiffness. Patients identified with high levels of vascular stiffness are most likely to benefit from strategies to reduce vascular oxidative stress.

aBHF Glasgow Cardiovascular Research Centre, University of Glasgow, UK

bDepartment of Cardiothoracic Surgery, Western Infirmary, UK

cDepartment of Vascular Surgery, Gartnavel General Hospital, Glasgow, UK

dGlasgow Cardiac Magnetic Resonance Unit, University of Glasgow, Glasgow, Scotland, UK

Received 5 October, 2007

Revised 13 December, 2007

Accepted 9 January, 2008

Correspondence to Professor Anna F. Dominiczak, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow, G12 8TA, Scotland, UK Tel: +44 (141) 330 5420; fax: +44 (141) 330 6997; e-mail: ad7e@clinmed.gla.ac.uk

© 2008 Lippincott Williams & Wilkins, Inc.