Absence of CD40 signaling is associated with an increase in intimal thickening after arterial injury.
Immune-mediator CD40 ligand is expressed on a variety of cell types involved in the immune response and on the cells of the vascular system. Inhibition of CD40 signaling has been associated with reduction of experimental atherosclerosis and transplant-associated vasculopathy. Immune response also plays a cardinal role in intimal thickening after acute arterial-wall injury. After carotid artery injury in CD40 ligand knockout (CD40L(-/-)) mice, the intimal thickening was increased 3-fold compared with the thickening in background B6/129 mice. The extent of thickening was similar to the thickening in B6/129 mice depleted of T lymphocytes with anti-CD4 and anti-CD8 antibodies. Injection of splenocytes from B6/129 mice into the CD40L(-/-) mice reduced the intimal thickening to the level comparable to the thickening in background B6/129 mice. These data suggest that CD40 signaling plays a significant role in the inhibitory effect of T lymphocytes on intimal thickening after arterial injury.
Division of Cardiology, Cedars-Sinai Medical Center/UCLA School of Medicine, Los Angeles, California, USA.
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Remskar
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Li
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Chyu
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Shah
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Cercek
D000818:Animals; D019013:CD40 Antigens / Q000502:physiology*; D023201:CD40 Ligand / Q000096:biosynthesis / Q000494:pharmacology; D002339:Carotid Arteries / Q000276:immunology / Q000473:pathology; D020212:Carotid Artery Injuries / Q000150:complications* / Q000473:pathology*; D003094:Collagen / Q000378:metabolism; D004347:Drug Interactions; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D008212:Lymphocyte Depletion; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D015398:Signal Transduction; D013154:Spleen / Q000737:chemistry / Q000166:cytology; D013601:T-Lymphocytes / Q000502:physiology; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis
D019013:CD40 Antigens; D019010:Vascular Cell Adhesion Molecule-1; D023201:CD40 Ligand; D003094:Collagen