Flow-mediated vasodilation is suggested as one of the mechanisms involved in arterial expansive remodelling, which is thought to be a defence mechanism in atherogenesis. In the present study, we tested the hypothesis that lumen obstructive plaque formation is associated with failure of NO (nitric oxide)-dependent vasodilation in conduit vessels. Cardiac function and aortic root flow velocities were assessed using high-resolution echocardiography and two-dimensional-guided pulsed Doppler in ApoE−/− (apolipoprotein E-deficient) mice fed a standard or high-cholesterol diet. Endothelial function in the proximal and mid-descending aortic regions was studied using a myograph technique. Flow velocity at the aortic root of cholesterol-fed ApoE−/− mice was significantly increased as a result of lumen narrowing, detected via histological analysis. NO-dependent vasodilatory responses were selectively impaired in the atherosclerosis-prone vascular regions in cholesterol-fed ApoE−/− mice. In conclusion, consumption of a high-cholesterol diet results in lumen obstructive plaque formation in ApoE−/− mice, which significantly alters aortic root haemodynamics. This phenomenon is associated with impaired NO-dependent vasodilation in vessel segments known to be prone to atherosclerosis.
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Research Article|
May 24 2005
Haemodynamically significant plaque formation and regional endothelial dysfunction in cholesterol-fed ApoE−/− mice
Maria E. JOHANSSON;
Maria E. JOHANSSON
1
*Department of Physiology, Institute of Physiology and Pharmacology, The Sahlgrenska Academy, Göteborg University, Göteborg, Sweden
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Ulrika HÄGG;
Ulrika HÄGG
1
*Department of Physiology, Institute of Physiology and Pharmacology, The Sahlgrenska Academy, Göteborg University, Göteborg, Sweden
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Johannes WIKSTRÖM;
Johannes WIKSTRÖM
*Department of Physiology, Institute of Physiology and Pharmacology, The Sahlgrenska Academy, Göteborg University, Göteborg, Sweden
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Anna WICKMAN;
Anna WICKMAN
*Department of Physiology, Institute of Physiology and Pharmacology, The Sahlgrenska Academy, Göteborg University, Göteborg, Sweden
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Göran BERGSTRÖM;
Göran BERGSTRÖM
*Department of Physiology, Institute of Physiology and Pharmacology, The Sahlgrenska Academy, Göteborg University, Göteborg, Sweden
†Department of Clinical Physiology, Institute of Cardiovascular Disease, The Sahlgrenska Academy, Göteborg University, Göteborg, Sweden
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Li-ming GAN
*Department of Physiology, Institute of Physiology and Pharmacology, The Sahlgrenska Academy, Göteborg University, Göteborg, Sweden
†Department of Clinical Physiology, Institute of Cardiovascular Disease, The Sahlgrenska Academy, Göteborg University, Göteborg, Sweden
Correspondence: Dr Li-ming Gan, Department of Physiology, Institute of Physiology and Pharmacology, The Sahlgrenska Academy, Göteburg University, Göteburg, Sweden (email li-ming.gan@hjl.gu.se).
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Publisher: Portland Press Ltd
Received:
November 04 2004
Revision Received:
January 13 2005
Accepted:
January 28 2005
Accepted Manuscript online:
January 28 2005
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society
2005
Clin Sci (Lond) (2005) 108 (6): 531–538.
Article history
Received:
November 04 2004
Revision Received:
January 13 2005
Accepted:
January 28 2005
Accepted Manuscript online:
January 28 2005
Citation
Maria E. JOHANSSON, Ulrika HÄGG, Johannes WIKSTRÖM, Anna WICKMAN, Göran BERGSTRÖM, Li-ming GAN; Haemodynamically significant plaque formation and regional endothelial dysfunction in cholesterol-fed ApoE−/− mice. Clin Sci (Lond) 1 June 2005; 108 (6): 531–538. doi: https://doi.org/10.1042/CS20040322
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