Souza Alexandre W S de, de Leeuw Karina, van Timmeren Mirjan M, Limburg Pieter C, Stegeman Coen A, Bijl Marc, Westra Johanna, Kallenberg Cees G M
Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; Rheumatology Division, Universidade Federal de São Paulo/Escola Paulista de Medicina (Unifesp/EPM), São Paulo-SP, Brazil.
Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
PLoS One. 2014 Apr 28;9(4):e96067. doi: 10.1371/journal.pone.0096067. eCollection 2014.
The objective of this study was to evaluate whether levels of high mobility group box 1 (HMGB1) in granulomatosis with polyangiitis (GPA) patients are associated with carotid atherosclerosis, related to levels of soluble receptor for advanced glycation end-products (sRAGE) and influenced by immunosuppressive or lipid-lowering therapy. Twenty-three GPA patients and 20 controls were evaluated for HMGB1- and sRAGE levels and for carotid atherosclerosis using ultrasound to determine intima-media thickness (IMT). In vitro the effect of atorvastatin on the production of HMGB1 by lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVEC) was assessed. Serum HMGB1 and sRAGE levels did not differ between patients and controls. A negative correlation was found between sRAGE and maximum IMT but HMGB1 and carotid IMT were not related. HMGB1 levels were reduced in GPA patients on statins and prednisolone. In vitro, atorvastatin reduced HMGB1 levels in supernatants of activated HUVEC. In conclusion, carotid IMT is inversely correlated with sRAGE levels but not with HMGB1 levels. Statins and prednisolone are associated with reduced serum HMGB1 levels and atorvastatin decreases HMGB1 release by activated HUVEC in vitro, indicating an additional anti-inflammatory effect of statins.
本研究的目的是评估肉芽肿性多血管炎（GPA）患者的高迁移率族蛋白B1（HMGB1）水平是否与颈动脉粥样硬化相关，是否与晚期糖基化终产物可溶性受体（sRAGE）水平有关，以及是否受免疫抑制或降脂治疗的影响。对23例GPA患者和20例对照者进行了HMGB1和sRAGE水平评估，并使用超声测定内膜中层厚度（IMT）以评估颈动脉粥样硬化情况。在体外，评估了阿托伐他汀对脂多糖（LPS）刺激的人脐静脉内皮细胞（HUVEC）产生HMGB1的影响。患者和对照者的血清HMGB1和sRAGE水平无差异。发现sRAGE与最大IMT呈负相关，但HMGB1与颈动脉IMT无关。服用他汀类药物和泼尼松龙的GPA患者的HMGB1水平降低。在体外，阿托伐他汀降低了活化的HUVEC上清液中的HMGB1水平。总之，颈动脉IMT与sRAGE水平呈负相关，但与HMGB1水平无关。他汀类药物和泼尼松龙与血清HMGB1水平降低有关，且阿托伐他汀在体外可降低活化的HUVEC释放HMGB1，表明他汀类药物具有额外的抗炎作用。
