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Atherogenesis in mice does not require CD40 ligand from bone marrow-derived cells
Udo Bavendiek1, Andreas Zirlik, Samantha LaClair
1Donald W. Reynolds Cardiovascular Clinical Research Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass02115, USA.
Arteriosclerosis, Thrombosis, and Vascular Biology
|March 5, 2005
Summary
CD40 ligand (CD40L) influences atherosclerosis development. Surprisingly, CD40L on non-hematopoietic cells, not immune cells, is key for this process in mice, impacting lesion composition and size.
Area of Science:
- Cardiovascular Biology
- Immunology
- Atherosclerosis Research
Background:
- CD40 ligand (CD40L) is implicated in atherosclerosis.
- The cellular origin of CD40L in this process is not well understood.
Purpose of the Study:
- To investigate the role of CD40L from hematopoietic cells in atherogenesis.
- To determine if CD40L on macrophages, lymphocytes, or platelets is critical for lesion development.
Main Methods:
- Utilized low-density lipoprotein receptor-deficient (ldlr-/-) and compound-mutant ldlr-/-/cd40l-/- mice.
- Performed bone marrow reconstitution experiments to assess cell-specific CD40L function.
Main Results:
- Systemic CD40L deficiency reduced atherosclerotic lesion development and altered lesion composition (fewer macrophages/lipids, more smooth muscle cells/collagen).
- Bone marrow reconstitution with CD40L-deficient cells did not significantly impact lesion size or composition, suggesting non-hematopoietic CD40L is crucial.
Conclusions:
- CD40L modulates atherogenesis in mice primarily through non-hematopoietic cell expression.
- This finding challenges the presumed role of immune cell-derived CD40L and has significant implications for understanding atherosclerosis pathophysiology and developing therapies.