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. 2000 Jun 20;97(13):7464-9.
doi: 10.1073/pnas.97.13.7464.

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

E Lutgens  1 , K B Cleutjens, S Heeneman, V E Koteliansky, L C Burkly, M J Daemen
Affiliations

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

E Lutgens et al. Proc Natl Acad Sci U S A. .

Abstract

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 beta1 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 beta.

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Figures

Figure 1
Figure 1
Quantification of plaque characteristics of both early and delayed anti-CD40L antibody- and control-treated apoE−/− mice. (a) Individual plaque area; (b) T-lymphocyte content; (c) macrophage content; (d) lipid core content; (e) collagen content; (f) ASMA content. ∗, P < 0.05, anti-CD40L antibody vs. control; #, P < 0.05, 17-wk control treatment group (age at which delayed treatment started) vs. delayed anti-CD40L antibody treatment group or delayed control treatment group.
Figure 2
Figure 2
Histological characteristics of delayed anti-CD40L antibody treatment. (a and b) Hematoxylin-and-eosin-stained longitudinal section of the aortic arch, including the brachiocephalic trunk, left carotid, and left subclavian artery (×25). Neither lesion area nor the number of lesions differed between anti-CD40L antibody- and control-treated mice. (c and d) Advanced atherosclerotic lesion, containing a lipid core and a fibrous cap. The relative lipid core area is less, and relative fibrous cap thickness is increased in anti-CD40L antibody- (d) compared to control-treated mice (c). (e and f) Sirius red staining of advanced atherosclerotic lesions, showing a higher relative collagen content in the anti-CD40L antibody-treated mouse (f) than in the control-treated mouse (e). (g and h) ASMA staining of advanced atherosclerotic lesions, showing a higher relative VSMC/myofibroblast content in the anti-CD40L-treated mouse (h) than in the control-treated mouse (g). (i and j) ED-1 staining of advanced atherosclerotic lesions, showing a decreased relative macrophage content in the anti-CD40L-treated mouse (j) compared to the control-treated mouse (i).
Figure 3
Figure 3
Anti-CD40L antibody treatment induces increased immunoreactivity of TGFβ1. (A and B) TGFβ1 immunostaining of advanced atherosclerotic lesions, showing an increased immunoreactivity of TGFβ1 in macrophages of the anti-CD40L antibody-treated mouse (B) compared with the control-treated mouse (A).
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References

    1. Foy T M, Aruffo A, Bajorath J, Buhlmann J E, Noelle R J. Annu Rev Immunol. 1996;14:591–617. - PubMed
    1. Aruffo A, Farrington M, Hollenbaugh D, Li X, Milatovich A, Nonoyama S, Bajorath J, Grosmaire L S, Stenkamp R, Neubauer M, et al. Cell. 1993;72:291–300. - PubMed
    1. Durie F H, Fava R A, Foy T M, Aruffo A, Ledbetter J A, Noelle R J. Science. 1993;261:1328–1330. - PubMed
    1. Gerritse K, Laman J D, Noelle R, Aruffo A, Ledbetter J A, Boersma W J A, Claassen E. Proc Natl Acad Sci USA. 1996;93:2499–2504. - PMC - PubMed
    1. Larsen C P, Elwood E T, Alexander D Z, Ritchie S C, Hendrix R, Tucker-Burder C, Cho H R, Aruffo A, Hollenbaugh D, Linsley P S, et al. Nature (London) 1996;381:434–438. - PubMed

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