Lipid Accumulation in CD11c-expressing Intimal Myeloid Cells Induces Chemokine Production Required for Leukocyte Recruitment to Early Atherosclerotic Lesions

• Main Author: Siu, Allan
• Other Authors: Cybulsky, Myron
• Language: en_ca
• Published: 2013
• Subjects: Atheroscleorsis; Leukocyte Recruitment; Intimal Myeloid Cells; CD11c; Lipid Accumulation; Chemokines; 0379
• Online Access: http://hdl.handle.net/1807/42935

Monocyte recruitment promotes the accumulation of myeloid foam cells in early atherosclerotic plaques. However, initial foam cells form prior to increased monocyte recruitment in hypercholesterolemic Ldlr-/- mice. These initial foam cells are derived from myeloid cells residing in the normal intima, and express integrin alphaX (CD11c). The goal of this thesis was to assess the role of initial foam cells in atherogenesis. The approach was to delete these cells by diphtheria toxin-induced apoptosis in Ldlr-/- bone marrow chimeras. Depletion of CD11c+ leukocytes resulted in significant reductions of intimal lipid accumulation, monocyte recruitment, intimal chemokine expression, but not endothelial cell adhesion molecule expression, at 10 and 21 days of hypercholesterolemia. These data suggest that lipid uptake by resident intimal CD11c-expressing myeloid cells during the earliest stages of atherosclerosis promotes chemokine production that is required for increased monocyte recruitment.