Expression of CD40 in vascular smooth muscle cells and macrophages is associated with early development of human atherosclerotic lesions

Atherogenesis in Mice Does Not Require CD40 Ligand From Bone Marrow–Derived Cells

“…[1][2][3] Cells of the arterial wall, such as ECs and SMCs, as well as blood cells such as mononuclear phagocytes, T lymphocytes, and platelets, can express functional CD40 and CD40L. 5,7,10,24,25 Notably, these cell types express increased levels of the ligand and receptor within human and experimental atheroma, [7][8][9] and ligation of CD40 on these cell types in vitro induces a range of inflammatory processes pivotal to the pathogenesis of atherosclerosis. 1,5,7,24,26,27 Additionally, in vivo studies in hypercholesterolemic mice support the relevance of CD40L in the pathogenesis of atherosclerosis.…”

“…1,5,6 In human as well as murine atherosclerotic lesions, the endothelium, SMC, M⌽, and T cells express CD40L and its receptor CD40. [7][8][9] Platelets also express functional CD40L. 10 In vivo studies using hypercholesterolemic mice demonstrated the importance of CD40L for the development and progression of atherosclerotic lesions.…”

New Markers of Inflammation and Endothelial Cell Activation

“…Immunohistochemistry studies revealed the presence of the CD40/CD40L signaling dyad within both early and advanced human atherosclerotic plaques. 45,46 The importance for CD40 signaling in atherosclerotic plaque development and evolution was demonstrated using LDL receptor-deficient mice that were fed a high-cholesterol diet. 47,48 By interrupting CD40 signaling in these mice, using a neutralizing anti-CD40L antibody, both the de novo formation and the further progression of established atherosclerotic lesions were drastically reduced.…”

CD40 Ligand–Dependent Tyrosine Nitration of Prostacyclin Synthase In Vivo

“…[1][2][3] CD40 and CD40L are expressed on endothelial cells, vascular smooth muscle cells, mononuclear cells, and platelets, and CD40-CD40L interaction has been shown to exhibit proinflammatory and proatherogenic effects in vitro and in vivo. 4,5 In addition to the cell-associated form, CD40L also exists in a soluble, biologically active form (sCD40L), which has similar proinflammatory effects on vascular cells. Interestingly, sCD40L is associated with acute coronary syndromes, 6,7 as well as hypercholesterolemia, 8 and elevated sCD40L levels predict an increased cardiovascular risk in healthy subjects.…”