vascular endothelial dysfunction in β-thalassemia occurs despite increased enos expression and preserved vascular smooth muscle cell reactivity to no血管内皮功能障碍在β-thalassemia发生尽管增加以挪士表达和保护血管平滑肌细胞反应.pdfVIP

Vascular Endothelial Dysfunction in b-Thalassemia Occurs Despite Increased eNOS Expression and Preserved Vascular Smooth Muscle Cell Reactivity to NO 1,2 2 2 2 1 Ekatherina Stoyanova , Marie Trudel , Hady Felfly , Wafaa Lemsaddek , Damien Garcia , Guy Cloutier1,3* 1 Laboratory of Biorheology and Medical Ultrasonics, University of Montreal Hospital Research Center, Montreal, Quebec, Canada, 2 Molecular Genetics and Development, Clinical Research Institute of Montreal, Montreal, Quebec, Canada, 3 Department of Radiology, Radio-Oncology and Nuclear Medicine; and Institute of Biomedical Engineering, University of Montreal, Montreal, Quebec, Canada Abstract Aims: The hereditary b-thalassemia major condition requires regular lifelong blood transfusions. Transfusion-related iron overloading has been associated with the onset of cardiovascular complications, including cardiac dysfunction and vascular anomalies. By using an untransfused murine model of b-thalassemia major, we tested the hypothesis that vascular endothelial dysfunction, alterations of arterial structure and of its mechanical properties would occur despite the absence of treatments. Methods and Results: Vascular function and structure were evaluated ex vivo. Compared to the controls, endothelium- dependent vasodilation with acetylcholine was blunted in mesenteric resistance arteries of b-thalassemic mice while the endothelium-independent vasodilator (sodium nitroprusside) produced comparable vessel dilation, indicating endothelial cell impairment with preserved smooth muscle cell reactivity to nitric oxide (NO). While these findings suggest a decrease in NO bioavailability, Western blotting showed