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Na+-H+ exchanger 1 determines atherosclerotic lesion acidification and promotes atherogenesis.


ABSTRACT: The pH in atherosclerotic lesions varies between individuals. IgE activates macrophage Na+-H+ exchanger (Nhe1) and induces extracellular acidification and cell apoptosis. Here, we show that the pH-sensitive pHrodo probe localizes the acidic regions in atherosclerotic lesions to macrophages, IgE, and cell apoptosis. In Apoe-/- mice, Nhe1-deficiency or anti-IgE antibody reduces atherosclerosis and blocks lesion acidification. Reduced atherosclerosis in Apoe-/- mice receiving bone marrow from Nhe1- or IgE receptor Fc?R1-deficient mice, blunted foam cell formation and signaling in IgE-activated macrophages from Nhe1-deficient mice, immunocomplex formation of Nhe1 and Fc?R1 in IgE-activated macrophages, and Nhe1-Fc?R1 colocalization in atherosclerotic lesion macrophages support a role of IgE-mediated macrophage Nhe1 activation in atherosclerosis. Intravenous administration of a near-infrared fluorescent pH-sensitive probe LS662, followed by coregistered fluorescent molecular tomography-computed tomography imaging, identifies acidic regions in atherosclerotic lesions in live mice, ushering a non-invasive and radiation-free imaging approach to monitor atherosclerotic lesions in live subjects.

SUBMITTER: Liu CL 

PROVIDER: S-EPMC6726618 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Na<sup>+</sup>-H<sup>+</sup> exchanger 1 determines atherosclerotic lesion acidification and promotes atherogenesis.

Liu Cong-Lin CL   Zhang Xian X   Liu Jing J   Wang Yunzhe Y   Sukhova Galina K GK   Wojtkiewicz Gregory R GR   Liu Tianxiao T   Tang Rui R   Achilefu Samuel S   Nahrendorf Matthias M   Libby Peter P   Guo Junli J   Zhang Jin-Ying JY   Shi Guo-Ping GP  

Nature communications 20190904 1


The pH in atherosclerotic lesions varies between individuals. IgE activates macrophage Na<sup>+</sup>-H<sup>+</sup> exchanger (Nhe1) and induces extracellular acidification and cell apoptosis. Here, we show that the pH-sensitive pHrodo probe localizes the acidic regions in atherosclerotic lesions to macrophages, IgE, and cell apoptosis. In Apoe<sup>-/-</sup> mice, Nhe1-deficiency or anti-IgE antibody reduces atherosclerosis and blocks lesion acidification. Reduced atherosclerosis in Apoe<sup>-/-  ...[more]

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