DISCOVERIES (ISSN 2359-7232), 2015, January-March issue
Kubo N, McCurdy S, Boisvert WA. Defective Fas Expression on Bone Marrow Derived Cells Alters Atherosclerotic Plaque Morphology in Hyperlipidemic Mice. Discoveries 2015, Jan-Mar; 3(1): e37. DOI: 10.15190/d.2015.29
Submitted: February 12, 2015; Revised: March 23, 2015; Accepted: March 25, 2015; Published: March 31, 2015;
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Defective Fas Expression on Bone Marrow Derived Cells Alters Atherosclerotic Plaque Morphology in Hyperlipidemic Mice
Nobuhiko Kubo (1), Sara McCurdy (2), William A. Boisvert (2,*)
(1) Department of Clinical Laboratory Medicine, Omiya Medical Center, Jichi Medical School, Japan;
(2) Center for Cardiovascular Research, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii, USA
*Correspondence to: William A. Boisvert, PhD, Center for Cardiovascular Research, University of Hawaii John A. Burns School of Medicine, 651 Ilalo Street, Honolulu, HI 96813, USA; Phone: (808) 692-1567; Fax: (808) 692-1973; E-mail: wab@hawaii.edu
Abstract
Fas (CD95) is a member of the TNF-receptor family expressed on a wide range of cells. Interaction of Fas with its receptor, Fas ligand (Fas-L), stimulates an intracellular cascade of events that leads to apoptosis. Because apoptosis of inflammatory cells plays a key role in atherosclerosis we sought to determine the role of Fas in the development of atherosclerosis by repopulating the bone marrow cells of atherosclerosis-prone low density lipoprotein receptor null (LDL-R-/-) mice with either cells from lpr mice (lpr-BMT) that have defective Fas expression or from control mice (WT-BMT). The lpr-BMT mice exhibited no peripheral blood Fas expression 4 weeks after BMT. After consuming an atherogenic diet for 16 weeks, lpr-BMT mice developed atherosclerotic lesions characterized by smaller fibrous area with thinner fibrous cap and less TUNEL-positive staining compared to WT-BMT mice, although overall lesion size in lpr-BMT mice was similar to that of WT-BMT mice. Examination of a series of human atherosclerotic lesions revealed that many Fas-positive cells were colocalized with CD68-positive macrophages. Although apoptotic cells were rarely observed in the foam cell-rich fatty streak lesions, apoptotic CD68-positive macrophages in advanced lesions were detected in areas rich with inflammatory cells near the necrotic core. These observations suggest that Fas expression by the macrophages in atherosclerotic lesions can influence the plaque morphology towards a more fibrous type
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