Department of Regenerative Medicine and Cell biology

Research in Focus

Involvement of Modified Lipoprotein Immune Complexes and Sphingolipids in Inflammation and Autoimmunity

Autoimmune diseases are associated with accelerated atherosclerosis and increased risk of cardiovascular complication. A critical event in the development of atherosclerosis is the transformation of macrophages into foam cells, whereby macrophages internalize oxidized LDL (oxLDL) and oxLDL immune complexes (oxLDL-IC) and transform into activated foam cells. Investigators in the laboratory of Dr. Samar Hammad have examined the development of vascular complications in the MRL/lpr lupus mouse model lacking the inducible nitric oxide synthase (iNOS; gene: NOS2). They found abundant accumulation of oxLDL-IC and sphingosine kinase 1 (SK1) surrounding foam cells in the adventitia. SK1 is the enzyme implicated in mediating pro-survival and inflammatory responses through the generation of the bioactive signaling molecule sphingosine 1-phosphate, the levels of which were elevated in the plasma of the mouse model. rif6
Immunohistochemistry of oxidized LDL immune complexes and sphingosine kinase 1 (SK1) in aortic lesions in the adventitia. The aorta stains positive for oxLDL (red in the endothelium and tunica media), and IgG (green); lesions infiltrated with lipid-laden macrophages (foam cells); Arrow denotes site of oxLDL immune complex accumulation (yellow). Inset, SK1 (brown) is present around the foam cells (arrow).

posted 9/28/2011

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