ArticleCellular immunology
Lack of nitric oxide synthases increases lipoprotein immune complex deposition in the aorta and elevates plasma sphingolipid levels in lupus.
Article in Cellular immunology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Inducible nitric oxide synthase and systemic lupus erythematosus: a systematic review and meta-analysis.BMC immunology · 2020Pooled it
- A Pilot Study to Determine if Vitamin D Repletion Improves Endothelial Function in Lupus Patients.The American journal of the medical sciences · 2015Trial
- Hyperglycemia and Alteration in Sphingolipids Are Early Mediators of Diabetic Kidney Disease: Role of Elongase 1.American journal of nephrology · 2026Article
- Functional Roles of the Complement Immune System in Cardiac Inflammation and Hypertrophy.International journal of molecular sciences · 2025Review
- Scavenger receptors: key players in the immunological puzzle of lupus.Frontiers in lupus · 2025Article
- Exacerbating effects of circadian rhythm disruption on the systemic lupus erythematosus.Lupus science & medicine · 2024Article
- Population-enriched innate immune variants may identify candidate gene targets at the intersection of cancer and cardio-metabolic disease.Frontiers in endocrinology · 2023Review
- The role of sphingosine-1-phosphate in the development and progression of Parkinson's disease.Frontiers in cellular neuroscience · 2023Review
- Plasma Sphingolipid Profile Associated With Subclinical Atherosclerosis and Clinical Disease Markers of Systemic Lupus Erythematosus: Potential Predictive Value.Frontiers in immunology · 2021Article
- Relationships between immune gene expression and circulating cytokine levels in wild house mice.Ecology and evolution · 2020Article
- Sphingolipids and Diagnosis, Prognosis, and Organ Damage in Systemic Lupus Erythematosus.Frontiers in immunology · 2020Review
- L-sepiapterin restores SLE serum-induced markers of endothelial function in endothelial cells.Lupus science & medicine · 2019Article
- Race disparity in blood sphingolipidomics associated with lupus cardiovascular comorbidity.PloS one · 2019Article
- IFN-α Negatively Regulates the Expression of Endothelial Nitric Oxide Synthase and Nitric Oxide Production: Implications for Systemic Lupus Erythematosus.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Accelerated vascular disease in systemic lupus erythematosus: role of macrophage.Clinical immunology (Orlando, Fla.) · 2015Review
- Proliferation of macrophages due to the inhibition of inducible nitric oxide synthesis by oxidized low-density lipoproteins.EXCLI journal · 2015Article
- Role of interferon alpha in endothelial dysfunction: insights into endothelial nitric oxide synthase-related mechanisms.The American journal of the medical sciences · 2014Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
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 vascular disease in NOS2 and NOS3 KO MRL/lpr mice maybe mediated by increased plasma triglycerides, ceramide and S1P; decreased plasma IL-10; and accumulation of oxLDL-IC in the vessel wall. The results expose possible new targets to mitigate lupus-associated complications.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.