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, macrophages, and CD4 T cells, thereby accelerating plaque progression.
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, macrophages, and CD4 T cells, thereby accelerating plaque progression.
Authors: R Angelo de Claro; Xiaodong Zhu; Jingjing Tang; Vicki Morgan-Stevenson; Barbara R Schwartz; Akiko Iwata; W Conrad Liles; Elaine W Raines; John M Harlan Journal: Am J Pathol Date: 2011-05-06 Impact factor: 4.307
Authors: Amanda A Watkins; Kei Yasuda; Gabriella E Wilson; Tamar Aprahamian; Yao Xie; Elena Maganto-Garcia; Prachi Shukla; Lillian Oberlander; Bari Laskow; Hanni Menn-Josephy; Yuanyuan Wu; Pierre Duffau; Susan K Fried; Andrew H Lichtman; Ramon G Bonegio; Ian R Rifkin Journal: J Immunol Date: 2015-01-16 Impact factor: 5.422
Authors: Allison B Reiss; Kamran Anwar; Joan T Merrill; Edwin S L Chan; Nahel W Awadallah; Bruce N Cronstein; H Michael Belmont; Elise Belilos; Gary Rosenblum; Kristina Belostocki; Lois Bonetti; Kowser Hasneen; Steven E Carsons Journal: Rheumatol Int Date: 2009-06-23 Impact factor: 2.631