First Author | Liu CL | Year | 2019 |
Journal | Nat Commun | Volume | 10 |
Issue | 1 | Pages | 3978 |
PubMed ID | 31484936 | Mgi Jnum | J:279334 |
Mgi Id | MGI:6362266 | Doi | 10.1038/s41467-019-11983-3 |
Citation | Liu CL, et al. (2019) Na(+)-H(+) exchanger 1 determines atherosclerotic lesion acidification and promotes atherogenesis. Nat Commun 10(1):3978 |
abstractText | 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 FcepsilonR1-deficient mice, blunted foam cell formation and signaling in IgE-activated macrophages from Nhe1-deficient mice, immunocomplex formation of Nhe1 and FcepsilonR1 in IgE-activated macrophages, and Nhe1-FcepsilonR1 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. |