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Ghita Harifi Wared Nour-Eldine Mohammad Hassan A. Noureldine Mohammad Baker Berjaoui Romy Kallas Rita Khoury Imad Uthman Jamal Al-Saleh Munther A. Khamashta 《Autoimmunity reviews》2018,17(3):256-266
First described in 1983, antiphospholipid syndrome (APS) is an autoimmune condition characterized by the occurrence of recurrent arterial and/or venous thrombosis, and/or pregnancy morbidity, in the setting of persistent presence of antiphospholipid antibodies (aPL). While thrombosis is the most well-known pathogenic mechanism in this disorder, the relevance of some other mechanisms such as arterial stenosis is being increasingly recognized. Arterial stenosis has been first described in the renal arteries in patients with APS, however intracranial and coeliac arteries can also be involved with various and treatable clinical manifestations. The underlying pathophysiology of this stenotic arterial vasculopathy is not fully understood but some recent studies revealed new insights into the molecular mechanism behind this endothelial cell activation in APS. In this review, we discuss these newly discovered mechanisms and highlight the diagnostic and therapeutic modalities of the APS related arterial stenosis. 相似文献
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Lynda Zeboudj Mikael Maître Lea Guyonnet Ludivine Laurans Jeremie Joffre Jeremie Lemarie Simon Bourcier Wared Nour-Eldine Coralie Guérin Jonas Friard Abdelilah Wakkach Elizabeth Fabre Alain Tedgui Ziad Mallat Pierre-Louis Tharaux Hafid Ait-Oufella 《Journal of the American College of Cardiology》2018,71(2):160-172
Background
Several epidermal growth factor receptor (EGFR) inhibitors have been successfully developed for the treatment of cancer, limiting tumor growth and metastasis. EGFR is also expressed by leukocytes, but little is known about its role in the modulation of the immune response.Objectives
The aim of this study was to determine whether EGFR expressed on CD4+ T cells is functional and to address the consequences of EGFR inhibition in atherosclerosis, a T cell–mediated vascular chronic inflammatory disease.Methods
The authors used EGFR tyrosine kinase inhibitors (AG-1478, erlotinib) and chimeric Ldlr-/-Cd4-Cre/Egfrlox/lox mouse with a specific deletion of EGFR in CD4+ T cells.Results
Mouse CD4+ T cells expressed EGFR, and the EGFR tyrosine kinase inhibitor AG-1478 blocked in vitro T cell proliferation and Th1/Th2 cytokine production. In vivo, treatment of Ldlr–/– mice with the EGFR inhibitor erlotinib induced T cell anergy, reduced T cell infiltration within atherosclerotic lesions, and protected against atherosclerosis development and progression. Selective deletion of EGFR in CD4+ T cells resulted in decreased T cell proliferation and activation both in vitro and in vivo, as well as reduced interferon-γ, interleukin-4, and interleukin-2 production. Atherosclerotic lesion size was reduced by 2-fold in irradiated Ldlr–/– mice reconstituted with bone marrow from Cd4-Cre/Egfrlox/lox mice, compared to Cd4-Cre/Egfr+/+ chimeric mice, after 4, 6, and 12 weeks of high-fat diet, associated with marked reduction in T cell infiltration in atherosclerotic plaques. Human blood T cells expressed EGFR and EGFR inhibition reduced T cell proliferation both in vitro and in vivo.Conclusions
EGFR blockade induced T cell anergy in vitro and in vivo and reduced atherosclerosis development. Targeting EGFR may be a novel strategy to combat atherosclerosis. 相似文献3.
Mohammad Hassan A. Noureldine Wared Nour-Eldine Munther A. Khamashta Imad Uthman 《Seminars in arthritis and rheumatism》2019,48(5):860-866
The Antiphospholipid syndrome (APS), formerly known as Anticardiolipin or Hughes syndrome, is a systemic autoimmune disorder characterized by obstetrical complications and thrombotic events affecting almost every organ-system in patients persistently testing positive for antiphospholipid antibodies (aPL). The contribution of the extra-criteria aPL to the pathogenesis of APS have exceeded the expectations of a simple, direct pathologic ‘hit’ leading to thrombogenesis or obstetrical complications, and more pathologic pathways are being linked directly or indirectly to aPL. The value of extra-criteria aPL is on the rise, and these antibodies are nowadays evaluated as markers for risk assessment in the diagnostic approach to APS. A diagnosis of APS should be considered in pediatric patients with suggestive clinical and laboratory picture. Management of APS remains mostly based on anticoagulation, while other drugs are being tested for efficacy and side effects. Low-dose aspirin may have a role in the management of thrombotic and obstetric APS. Due to the high variability in disease severity and complication recurrence outcomes, new tools are being developed and validated to assess the damage index and quality of life of APS patients. 相似文献
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Gasoline fume inhalation induces apoptosis,inflammation, and favors Th2 polarization in C57BL/6 mice
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