Differences in Endothelial Activation and Dysfunction Induced by Antiphospholipid Antibodies Among Groups of Patients With Thrombotic, Refractory, and Non-refractory Antiphospholipid Syndrome

被引:11
作者
Velasquez, Manuela [1 ]
Pelaez, Luisa F. [1 ]
Rojas, Mauricio [2 ]
Narvaez-Sanchez, Raul [3 ]
Velasquez, Jesus A. [4 ]
Escudero, Carlos [5 ,6 ,7 ]
San Martin, Sebastian [5 ,7 ,8 ]
Cadavid, Angela P. [1 ,5 ,9 ]
机构
[1] Univ Antioquia UdeA, Fac Med, Grp Reprod, Dept Microbiol & Parasitol, Medellin, Colombia
[2] Univ Antioquia UdeA, Fac Med, Grp Inmunol Celular & Inmunogenet, Unidad Citometr Flujo,Sede Invest Univ, Medellin, Colombia
[3] Univ Antioquia UdeA, Fac Med, Physiol & Biochem Res Grp Physis, Medellin, Colombia
[4] Hosp Univ San Vicente Fdn, Medellin, Colombia
[5] Red Iberoame Alterc Vasc Asoc & TRanstomos EMbara, Chillan, Chile
[6] Univ Bio Bio, Fac Sci, Vasc Physiol Lab, Dept Basic Sci, Chillan, Chile
[7] Grp Res & Innovat Vasc Hlth GRIVAS Hlth, Chillan, Chile
[8] Univ Valparaiso, Biomed Res Ctr, Sch Med, Valparaiso, Chile
[9] Univ Antioquia UdeA, Fac Med, Grp Invest Trombosis, Medellin, Colombia
关键词
antiphospholipid syndrome; endothelial cells; endothelial activation and dysfunction; beta 2-glycoprotein I; immunoglobulin G; antiphosholipid syndrome; NITRIC-OXIDE; OXIDATIVE STRESS; MICROPARTICLES; HYDROXYCHLOROQUINE; PREGNANCY; IGG; BINDING; EVENTS; UPDATE; CELLS;
D O I
10.3389/fphys.2021.764702
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by pregnancy morbidity or thrombosis and persistent antiphospholipid antibodies (aPL) that bind to the endothelium and induce endothelial activation, which is evidenced by the expression of adhesion molecules and the production of reactive oxygen species (ROS) and subsequent endothelial dysfunction marked by a decrease in the synthesis and release of nitric oxide (NO). These endothelial alterations are the key components for the development of severe pathological processes in APS. Patients with APS can be grouped according to the presence of other autoimmune diseases (secondary APS), thrombosis alone (thrombotic APS), pregnancy morbidity (obstetric APS), and refractoriness to conventional treatment regimens (refractory APS). Typically, patients with severe and refractory obstetric APS exhibit thrombosis and are classified as those having primary or secondary APS. The elucidation of the mechanisms underlying these alterations according to the different groups of patients with APS could help establish new therapies, particularly necessary for severe and refractory cases. Therefore, this study aimed to evaluate the differences in endothelial activation and dysfunction induced by aPL between patients with refractory obstetric APS and other APS clinical manifestations. Human umbilical vein endothelial cells (HUVECs) were stimulated with polyclonal immunoglobulin-G (IgG) from different groups of patients n = 21), including those with primary (VTI) and secondary thrombotic APS (VTII) and refractory primary (RI+), refractory secondary (RII+), and non-refractory primary (NR+) obstetric APS. All of them with thrombosis. The expression of adhesion molecules; the production of ROS, NO, vascular endothelial growth factor (VEGF), and endothelin-1; and the generation of microparticles were used to evaluate endothelial activation and dysfunction. VTI IgG induced the expression of adhesion molecules and the generation of microparticles and VEGF. RI+ IgG induced the expression of adhesion molecules and decreased NO production. RII+ IgG increased the production of microparticles, ROS, and endothelin-1 and reduced NO release. NR+ IgG increased the production of microparticles and endothelin-1 and decreased the production of VEGF and NO. These findings reveal differences in endothelial activation and dysfunction among groups of patients with APS, which should be considered in future studies to evaluate new therapies, especially in refractory cases.
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页数:17
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