Lack of nitric oxide synthases increases lipoprotein immune complex deposition in the aorta and elevates plasma sphingolipid levels in lupus.

Cellular Immunology
Mohammed M Al GadbanSamar M Hammad

Abstract

Systemic lupus erythematosus (SLE) patients display impaired endothelial nitric oxide synthase (eNOS) function required for normal vasodilatation. SLE patients express increased compensatory activity of inducible nitric oxide synthase (iNOS) generating excess nitric oxide that may result in inflammation. We examined the effects of genetic deletion of NOS2 and NOS3, encoding iNOS and eNOS respectively, on accelerated vascular disease in MRL/lpr lupus mouse model. NOS2 and NOS3 knockout (KO) MRL/lpr mice had higher plasma levels of triglycerides (23% and 35%, respectively), ceramide (45% and 21%, respectively), and sphingosine 1-phosphate (S1P) (21%) compared to counterpart MRL/lpr controls. Plasma levels of the anti-inflammatory cytokine interleukin 10 (IL-10) in NOS2 and NOS3 KO MRL/lpr mice were lower (53% and 80%, respectively) than counterpart controls. Nodule-like lesions in the adventitia were detected in aortas from both NOS2 and NOS3 KO MRL/lpr mice. Immunohistochemical evaluation of the lesions revealed activated endothelial cells and lipid-laden macrophages (foam cells), elevated sphingosine kinase 1 expression, and oxidized low-density lipoprotein immune complexes (oxLDL-IC). The findings suggest that advanced vascula...Continue Reading

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Citations

Sep 10, 2015·The American Journal of the Medical Sciences·Diane L Kamen, Jim C Oates
May 7, 2014·The American Journal of the Medical Sciences·Joy N Jones Buie, Jim C Oates
Feb 2, 2015·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Mohammed M Al GadbanSamar M Hammad
Aug 6, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Joy Jones BuieJim C Oates
Jun 7, 2019·Lupus Science & Medicine·Joy N Jones BuieJim C Oates
Jan 5, 2021·Ecology and Evolution·Stuart YoungJanette E Bradley
Jun 13, 2021·Autoimmunity Reviews·Kun XiangDe-Guang Wang
Aug 6, 2021·Prostaglandins & Other Lipid Mediators·Jihua TianYun Zhou

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