Both early and delayed anti-CD40L antibody treatment induces a stable plaque phenotype

Esther Lutgens, Kitty B.J.M. Cleutjens, Sylvia Heeneman, Victor E. Koteliansky, Linda C. Burkly, Mat J.A.P. Daemen

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In the present study, we investigated the role of the CD40L-CD40 pathway in a model of progressive atherosclerosis. ApoE(-/-) mice were treated with an anti-CD40L antibody or a control antibody for 12 wk. Antibody treatment started early (age 5 wk) or was delayed until after the establishment of atherosclerosis (age 17 wk). In both the early and delayed treatment groups, anti-CD40L antibody did not decrease plaque area or inhibit lesion initiation or age-related increase in lesion area. The morphology of initial lesions was not affected, except for a decrease in T-lymphocyte content. Effects of anti- CD40L antibody treatment on the morphology of advanced lesions were pronounced. In both the early and delayed treatment groups, T-lymphocyte content was significantly decreased. Furthermore, a pronounced increase in collagen content, vascular smooth muscle cell/myofibroblast content, and fibrous cap thickness was observed. In the delayed treatment group, a decrease in lipid core and macrophage content occurred. Interestingly, advanced lesions of anti-CD40L antibody-treated mice exhibited an increased transforming growth factor β1 immunoreactivity, especially in macrophages. In conclusion, both early and delayed treatment with an anti-CD40L antibody do not affect atherosclerotic lesion initiation but do result in the development of a lipid-poor collagen-rich stable plaque phenotype. Furthermore, delayed treatment with anti-CD40L antibody can transform the lesion profile from a lipid-rich to a lipid-poor collagen-rich phenotype. Postulated mechanisms of this effect on plaque phenotype are the down- regulation of proinflammatory pathways and up-regulation of collagen- promoting factors like transforming growth factor β.

Original languageEnglish (US)
Pages (from-to)7464-7469
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number13
StatePublished - Jun 20 2000

ASJC Scopus subject areas

  • General


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