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. 2005 Jun;25(6):1244-9.
doi: 10.1161/01.ATV.0000161420.55482.ef. Epub 2005 Mar 3.

Atherogenesis in mice does not require CD40 ligand from bone marrow-derived cells

Udo Bavendiek  1 , Andreas Zirlik, Samantha LaClair, Lindsey MacFarlane, Peter Libby, Uwe Schönbeck
Affiliations

Atherogenesis in mice does not require CD40 ligand from bone marrow-derived cells

Udo Bavendiek et al. Arterioscler Thromb Vasc Biol. 2005 Jun.

Abstract

Objective: Recent research suggests a central role for CD40 ligand (CD40L) in atherogenesis. However, the relevant cellular source of this proinflammatory cytokine remains unknown. To test the hypothesis that CD40L expressed on hematopoietic cell types (eg, macrophages, lymphocytes, platelets) is crucial to atherogenesis, we performed bone marrow reconstitution experiments using low-density receptor-deficient (ldlr-/-) and ldlr-/-/cd40l-/- compound-mutant mice.

Methods and results: As expected, systemic lack of CD40L in hypercholesterolemic ldlr-/- mice significantly reduced the development of atherosclerotic lesions in the aortic arch, aortic root, and abdominal aorta compared with ldlr-/- mice. Furthermore, atheromata in ldlr-/-/cd40l-/- mice showed reduced accumulation of macrophages and lipids and increased content in smooth muscle cells and collagen compared with ldlr-/- mice. Surprisingly, reconstitution of irradiated ldlr-/- mice with ldlr-/-/cd40l-/- bone marrow did not affect the size or composition of atherosclerotic lesions in the root or arch of hypercholesterolemic ldlr-/- mice. Moreover, lipid deposition in the abdominal aorta diminished only marginally compared with mouse aortas reconstituted with ldlr-/- bone marrow.

Conclusions: These experiments demonstrate that CD40L modulates atherogenesis, at least in mice, primarily by its expression on nonhematopoietic cell types rather than monocytes, T lymphocytes, or platelets, a surprising finding with important pathophysiologic and therapeutic implications.

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Comment in

  • CD40 ligand: not bad to the bone (marrow), after all.
    Ajijola OA, Goldschmidt-Clermont PJ, Satterwhite LL. Ajijola OA, et al. Arterioscler Thromb Vasc Biol. 2005 Jun;25(6):1088-90. doi: 10.1161/01.ATV.0000169538.64914.70. Arterioscler Thromb Vasc Biol. 2005. PMID: 15923539 No abstract available.

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