on April 19, 2007
Published online before print April 19, 2007, doi: 10.1161/ATVBAHA.107.142430
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Submitted on October 26, 2006
Accepted on March 29, 2007
Enhanced Immune System Activation and Arterial Inflammation Accelerates Atherosclerosis in Lupus-Prone Mice
Emmanuel L. Gautier ;
From INSERM Unit 551, UPMC-Paris 6, Dyslipoproteinemia and Atherosclerosis Research Unit, Hôpital de la Pitié, Paris, France.
* To whom correspondence should be addressed. E-mail: lesnik{at}chups.jussieu.fr.
Objective--Premature atherosclerosis is a characteristic feature of systemic lupus erythematosus, a prototypic autoimmune disease. The principle cellular and molecular mechanisms which underlie such accelerated atherosclerosis are indeterminate.
Methods and Results--The pathophysiology of lupus-mediated atherogenesis was evaluated in a novel animal model involving transplantation of bone marrow cells from the lupus prone strain gld into Ldl-r-/- mice. Diet-induced atherogenesis in lethally-irradiated Ldl-r-/- mice transplanted with gld bone marrow cells resulted in accelerated atherosclerosis (+65%) as compared with control mice transplanted with wild-type marrow cells. Enhanced atherogenesis was associated with enhanced activation of both B and T lymphocytes and with arterial inflammation involving endothelial cell activation, monocyte recruitment, and accumulation of apoptotic debris, macrophages, and CD4 T cells, but was independent of plasma lipid levels and renal function.
Conclusions--Our data support the contention that despite the absence of both disturbed cholesterol homeostasis and renal dysfunction in autoimmune gld
Ldl-r-/- mice, lupus disease induces enhanced activation of the immune system and acts locally on the vasculature to induce inflammation, together with accumulation of apoptotic debris, macrophage, and CD4 T cells, thereby accelerating plaque progression.
Key words: atherosclerosis • lupus • arterial inflammation • immune system • apoptotic cells
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