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Updated: Feb 19, 2026
Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
The cathelicidin protein CRAMP is a potential atherosclerosis self-antigen in ApoE(-/-) mice
Peter M Mihailovic1, Wai Man Lio1, Juliana Yano1
1Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Heart Institute, Los Angeles, California, United States of America.
Insights
The antimicrobial peptide CRAMP acts as a self-antigen in atherosclerosis. Low-dose CRAMP reduced disease, while high-dose CRAMP worsened atherosclerosis and inflammation in ApoE(-/-) mice.
Area of Science:
- Immunology
- Cardiovascular Research
- Autoimmunity
Background:
- Autoimmunity contributes to inflammation in atherosclerosis.
- The antimicrobial peptide LL-37, a fragment of hCAP18, is an autoantigen in psoriasis.
- Psoriasis is linked to coronary artery disease, suggesting potential links to atherosclerosis.
Purpose of the Study:
- To investigate the role of CRAMP, the mouse homolog of hCAP18, as a potential autoantigen in atherosclerosis.
- To determine the effects of CRAMP stimulation on immune cells in atherosclerosis-prone mice.
Main Methods:
- Used a truncated form of mouse CRAMP (tCRAMP) to stimulate splenocytes from ApoE(-/-) mice.
- Administered different doses of a shortened CRAMP peptide to ApoE(-/-) mice.
- Analyzed T cell phenotypes, neutrophil infiltration, CD8+ T cell degranulation, and conventional dendritic cell (cDC) populations.
Main Results:
- tCRAMP stimulation increased CD8+ T cells with Central Memory and Effector Memory phenotypes in ApoE(-/-) mice.
- Low-dose CRAMP immunization reduced atherosclerosis, while high-dose CRAMP exacerbated it, increasing neutrophil infiltration.
- Low-dose CRAMP increased splenic CD8+ T cell degranulation and reduced cDCs; high-dose CRAMP increased cDCs.
Conclusions:
- Identified CRAMP as a potential self-antigen involved in the immune response to atherosclerosis.
- Demonstrated dose-dependent effects of CRAMP immunization on atherosclerosis severity and immune cell profiles in ApoE(-/-) mice.
Abstract:
Auto-immunity is believed to contribute to inflammation in atherosclerosis. The antimicrobial peptide LL-37, a fragment of the cathelicidin protein precursor hCAP18, was previously identified as an autoantigen in psoriasis. Given the reported link between psoriasis and coronary artery disease, the biological relevance of the autoantigen to atherosclerosis was tested in vitro using a truncated (t) form of the mouse homolog of hCAP18, CRAMP, on splenocytes from athero-prone ApoE(-/-) mice. Stimulation with tCRAMP resulted in increased CD8+ T cells with Central Memory and Effector Memory phenotypes in ApoE(-/-) mice, differentially activated by feeding with normal chow or high fat diet. Immunization of ApoE(-/-) with different doses of the shortened peptide (Cramp) resulted in differential outcomes with a lower dose reducing atherosclerosis whereas a higher dose exacerbating the disease with increased neutrophil infiltration of the atherosclerotic plaques. Low dose Cramp immunization also resulted in increased splenic CD8+ T cell degranulation and reduced CD11b+CD11c+ conventional dendritic cells (cDCs), whereas high dose increased CD11b+CD11c+ cDCs. Our results identified CRAMP, the mouse homolog of hCAP-18, as a potential self-antigen involved in the immune response to atherosclerosis in the ApoE(-/-) mouse model.
