|NAGARAJAN, SHANUMGAM - Arkansas Children'S Nutrition Research Center (ACNC)
Submitted to: Journal of Immunology
Publication Type: Abstract Only
Publication Acceptance Date: 3/5/2009
Publication Date: 5/15/2009
Citation: Nagarajan, S. 2009. Loss of Fcgamma receptors ameliorates initiation and progression of atherosclerosis in hyperlipidemic mouse model [abstract]. Journal of Immunology. 182(Meeting Abstracts 1):94.24.
Technical Abstract: OxLDL generated during hyperlipidemia is known to induce an autoimmune response resulting in the production of anti-oxLDL IgG. In humans and in the hyperlipidemic mouse model, the titer of autoantibodies against oxLDL correlates with the progression of atherosclerosis. Although the presence of anti-oxLDL IgG is well documented, the contribution of FcRs to the initiation and/or progression of atherosclerosis has not been studied in detail. First, to address the presence of oxLDL-IC in atherosclerotic lesions, descending aorta from wild type (WT) and apoE ko mice fed chow diet for 18 weeks and oxLDL-IC in the lysates were determined. OxLDL-IC was detected in the aortic lysates of both WT and apoE ko mice. However, the levels were elevated about 8 fold in apoE ko mice. The presence of anti-oxLDL IgG in atherosclerotic lesions in patients and animal models, suggests the possibility of oxLDL-IC deposition in the lesions. To determine the role of FcRs in the initiation and/or progression of atherosclerosis, we have generated apoE ko gamma chain ko mice by mating gamma chain ko mice with apoE ko mice. ApoE ko and apoE ko gamma chain ko mice (age 4 wk) were fed chow diet for 20 weeks. Plasma cholesterol levels were similar in apoE ko and apoE ko gamma chain ko mice. Atherosclerotic lesions in aortic sinus were determined by staining cryosections with Oil Red O. Enface analysis of the descending aorta was performed by staining descending aorta from the aortic arch to the iliac bifurcation with Sudan IV. Both analyses showed about a 50% reduction in lesions in apoE ko gamma chain ko mice compared to apoE ko mice. These novel findings suggest activating FcRs contribute to the progression of atherosclerosis.