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

Author

Listed:
  • Cong-Lin Liu

    (the First Affiliated Hospital of Zhengzhou University
    Brigham and Women’s Hospital and Harvard Medical School)

  • Xian Zhang

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Jing Liu

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Yunzhe Wang

    (the First Affiliated Hospital of Zhengzhou University
    Brigham and Women’s Hospital and Harvard Medical School)

  • Galina K. Sukhova

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Gregory R. Wojtkiewicz

    (Harvard Medical School)

  • Tianxiao Liu

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Rui Tang

    (Washington University School of Medicine)

  • Samuel Achilefu

    (Washington University School of Medicine)

  • Matthias Nahrendorf

    (Harvard Medical School)

  • Peter Libby

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Junli Guo

    (Brigham and Women’s Hospital and Harvard Medical School
    Hainan Medical University)

  • Jin-Ying Zhang

    (the First Affiliated Hospital of Zhengzhou University)

  • Guo-Ping Shi

    (the First Affiliated Hospital of Zhengzhou University
    Brigham and Women’s Hospital and Harvard Medical School
    Hainan Medical University)

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 FcεR1-deficient mice, blunted foam cell formation and signaling in IgE-activated macrophages from Nhe1-deficient mice, immunocomplex formation of Nhe1 and FcεR1 in IgE-activated macrophages, and Nhe1-FcεR1 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.

Suggested Citation

  • Cong-Lin Liu & Xian Zhang & Jing Liu & Yunzhe Wang & Galina K. Sukhova & Gregory R. Wojtkiewicz & Tianxiao Liu & Rui Tang & Samuel Achilefu & Matthias Nahrendorf & Peter Libby & Junli Guo & Jin-Ying Z, 2019. "Na+-H+ exchanger 1 determines atherosclerotic lesion acidification and promotes atherogenesis," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11983-3
    DOI: 10.1038/s41467-019-11983-3
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