Nature communications, 2019-09, Vol.10 (1), p.3978-14, Article 3978
2019
Details
- Autor(en) / Beteiligte
- Titel
- Na + -H + exchanger 1 determines atherosclerotic lesion acidification and promotes atherogenesis
- Ist Teil von
- Nature communications, 2019-09, Vol.10 (1), p.3978-14, Article 3978
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2019
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/s41467-019-11983-3Titel-ID: cdi_doaj_primary_oai_doaj_org_article_b0bd30f23bbe46f4ac1f69c4a193d1c1
- Format
- –
- Schlagworte
- Acidification, Acids - chemistry, Animals, Antibodies, Apolipoprotein E, Apolipoproteins E - deficiency, Apolipoproteins E - genetics, Apoptosis, Apoptosis - genetics, Arteriosclerosis, Atherogenesis, Atherosclerosis, Atherosclerosis - genetics, Atherosclerosis - metabolism, Bone marrow, Cell activation, Computed tomography, Fluorescence, Humans, Hydrogen, Hydrogen-Ion Concentration, Immunoglobulin E, Intravenous administration, Lesions, Macrophage Activation - genetics, Macrophages, Macrophages - metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Na+/H+-exchanging ATPase, pH effects, Plaque, Atherosclerotic - genetics, Plaque, Atherosclerotic - metabolism, Radiation, Signal Transduction - genetics, Sodium-Hydrogen Exchanger 1 - genetics, Sodium-Hydrogen Exchanger 1 - metabolism