Back to Search
Start Over
Lack of alpha CGRP exacerbates the development of atherosclerosis in ApoE-knockout mice.
- Source :
-
Scientific reports [Sci Rep] 2024 Aug 08; Vol. 14 (1), pp. 18377. Date of Electronic Publication: 2024 Aug 08. - Publication Year :
- 2024
-
Abstract
- The effects of calcitonin gene-related peptide (CGRP) on atherosclerosis remain unclear. We used apolipoprotein E-deficient (ApoE <superscript>-/-</superscript> ) mice to generate double-knockout ApoE <superscript>-/-</superscript> :CGRP <superscript>-/-</superscript> mice lacking alpha CGRP. ApoE <superscript>-/-</superscript> :CGRP <superscript>-/-</superscript> 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 <superscript>-/-</superscript> :CGRP <superscript>-/-</superscript> 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 <superscript>-/-</superscript> :CGRP <superscript>-/-</superscript> mice compared with mice treated with human IgG (5 mg/kg). We further examined whether results observed in ApoE <superscript>-/-</superscript> :CGRP <superscript>-/-</superscript> mice could similarly be obtained by administering a humanized monoclonal CGRP antibody, galcanezumab, to ApoE <superscript>-/-</superscript> mice. ApoE <superscript>-/-</superscript> 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.<br /> (© 2024. The Author(s).)
- Subjects :
- Animals
Mice
Diet, High-Fat adverse effects
Tumor Necrosis Factor-alpha metabolism
Male
Mice, Knockout, ApoE
Disease Models, Animal
Humans
Antibodies, Monoclonal, Humanized pharmacology
Etanercept pharmacology
Mice, Inbred C57BL
Cell Movement drug effects
Aorta metabolism
Aorta pathology
Aorta drug effects
Atherosclerosis metabolism
Atherosclerosis genetics
Atherosclerosis pathology
Calcitonin Gene-Related Peptide metabolism
Apolipoproteins E deficiency
Apolipoproteins E genetics
Plaque, Atherosclerotic pathology
Plaque, Atherosclerotic metabolism
Plaque, Atherosclerotic genetics
Mice, Knockout
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 14
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 39112593
- Full Text :
- https://doi.org/10.1038/s41598-024-69331-5