Lack of alpha CGRP exacerbates the development of atherosclerosis in ApoE-knockout mice.

Autor: Hashikawa-Hobara N; Department of Life Science, Okayama University of Science, 1-1 Ridai-Cho, Kita-Ku, Okayama, 700-0005, Japan. hashikawa-hobara@ous.ac.jp., Inoue S; Department of Life Science, Okayama University of Science, 1-1 Ridai-Cho, Kita-Ku, Okayama, 700-0005, Japan., Hashikawa N; Department of Life Science, Okayama University of Science, 1-1 Ridai-Cho, Kita-Ku, Okayama, 700-0005, Japan.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Aug 08; Vol. 14 (1), pp. 18377. Date of Electronic Publication: 2024 Aug 08.
DOI: 10.1038/s41598-024-69331-5
Abstrakt: The effects of calcitonin gene-related peptide (CGRP) on atherosclerosis remain unclear. We used apolipoprotein E-deficient (ApoE -/- ) mice to generate double-knockout ApoE -/- :CGRP -/- mice lacking alpha CGRP. ApoE -/- :CGRP -/- mice exhibited larger atherosclerotic plaque areas, peritoneal macrophages with enhanced migration functions, and elevated levels of the inflammatory cytokine tumor necrosis factor (TNF)-⍺. Thus, we also explored whether inhibiting TNF-⍺ could improve atherosclerosis in ApoE -/- :CGRP -/- mice by administering etanercept intraperitoneally once a week (5 mg/kg) alongside a high-fat diet for 2 weeks. This treatment led to significant reductions in aortic root lesion size, atherosclerotic plaque area and macrophage migration in ApoE -/- :CGRP -/- mice compared with mice treated with human IgG (5 mg/kg). We further examined whether results observed in ApoE -/- :CGRP -/- mice could similarly be obtained by administering a humanized monoclonal CGRP antibody, galcanezumab, to ApoE -/- mice. ApoE -/- mice were subcutaneously administered galcanezumab at an initial dose of 50 mg/kg, followed by a dose of 30 mg/kg in the second week. Galcanezumab administration did not affect systolic blood pressure, serum lipid levels, or macrophage migration but led to a significant increase in lipid deposition at the aortic root. These findings suggest that alpha CGRP plays a critical role in inhibiting the progression of atherosclerosis.
(© 2024. The Author(s).)
Databáze: MEDLINE
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