Cardiology Online - International Academy of Cardiology
»search site
The International Academy of Cardiology is dedicated to the advancement of global research in cardiovascular medicine through the support of scientific meetings and publications.
   Home Page
   Discussion Groups
   Job Opportunities
   Contact Us





21st World Congress on Heart Disease



Guo-Ping Shi, SC.D., D.SC., Brigham and Women’s Hospital and Harvard Medical School, Boston, USA


The pH in atherosclerotic lesions varies between individuals. Immunoglobulin E (IgE) activates the macrophage Na+-H+ exchanger (Nhe1), acidifies the extracellular milieu, and induces cell apoptosis. The pH-sensitive pHrodo probe identifies acidic regions in human and murine atherosclerotic lesions that colocalize with macrophages, IgE, and cell apoptosis. In apolipoprotein E (ApoE)-deficient mice, inactivation of Nhe1 reduces atherosclerotic lesion size, inflammation, tissue remodeling, and apoptosis. Nhe1 inactivation also blocks lesion acidification in regions rich in macrophages, IgE, and apoptosis. Intravenous administration of a near-infrared (NIR) fluorescent pH-sensitive probe LS662, followed by coregistered fluorescent molecular tomography-computed tomography (FMT-CT) imaging allows detection of acidic regions in atherosclerotic lesions in live mice and isolated thoracic-abdominal aortas. Lesions from Nhe1-inactivated mice have diminished acidity detected by pH-sensitive NIR fluorescence. Ex vivo pHrodo detection and immunohistochemical analysis following FMT-CT imaging establishes the colocalization of acidic regions with areas of macrophage accumulation, IgE expression, and apoptosis in atherosclerotic lesions. This study tests the role of Nhe1 in reducing atherosclerotic lesion pH and in promoting atherogenesis, and proposes a non-invasive and radiation-free imaging approach to localize and monitor the atherosclerotic lesions in live subjects.



©1998-2018 Cardiology Online, Inc. All rights reserved.
Cardiology Online is a registered trademark of Cardiology Online, Inc.