Grundtman Cecilia, Hollan Ivana, Førre Oystein T, Saatvedt Kjell, Mikkelsen Knut, Lundberg Ingrid E
Karolinska University Sola, Karolinska Institutet, Stockholm, Sweden.
Arthritis Rheum. 2010 Mar;62(3):667-73. doi: 10.1002/art.27264.
Various inflammatory rheumatic diseases (IRDs) are associated with increased mortality due to cardiovascular disease. The aim of this study was to investigate heart biopsy specimens obtained from patients undergoing coronary artery bypass grafting and compare markers of inflammation and endothelial cell activation in the cardiac and skeletal muscle of patients with and those without IRD.
Paired biopsy specimens of cardiac and skeletal muscle were obtained from 22 consecutive patients with IRD and 8 patients without IRD, all of whom were undergoing coronary artery bypass grafting. The biopsy specimens were evaluated in a blinded manner by conventional microscopy and digital image analysis for cell markers (CD3, CD4, CD8, CD68, CD163, and CD31), HLA (HLA-ABC, HLA-DR, and HLA-DQ), adhesion molecules (intercellular adhesion molecule 1 and vascular cell adhesion molecule 1), and proinflammatory cytokines (interleukin-1alpha, interleukin-1beta, and tumor necrosis factor).
Patients with IRD had significantly higher expression of adhesion molecules, proinflammatory cytokines, and all classes of HLA on cardiomyocytes and endothelial cells but no increase on mononuclear cells in the myocardium compared with patients without IRD. Furthermore, cardiac muscle from patients with IRD displayed significantly higher local expression of inflammation and activation of cardiac microvessels compared with skeletal muscle from the same patients.
Patients with cardiovascular disease had increased expression of adhesion molecules, HLA, and proinflammatory cytokines in heart tissue, indicating local inflammation involving microvessels and cardiomyocytes that could play a role in the pathogenesis of cardiovascular disease. The more pronounced changes in patients with IRD compared with patients without IRD might contribute to the increased risk of cardiovascular disease and premature death in patients with IRD.
多种炎性风湿性疾病(IRDs)与心血管疾病导致的死亡率增加相关。本研究的目的是调查接受冠状动脉搭桥术患者的心脏活检标本,并比较有无IRD患者心肌和骨骼肌中的炎症标志物及内皮细胞活化情况。
从22例连续的IRD患者和8例无IRD患者中获取成对的心肌和骨骼肌活检标本,所有患者均接受冠状动脉搭桥术。通过传统显微镜检查和数字图像分析以盲法评估活检标本中的细胞标志物(CD3、CD4、CD8、CD68、CD163和CD31)、HLA(HLA-ABC、HLA-DR和HLA-DQ)、黏附分子(细胞间黏附分子1和血管细胞黏附分子1)和促炎细胞因子(白细胞介素-1α、白细胞介素-1β和肿瘤坏死因子)。
与无IRD患者相比,IRD患者心肌细胞和内皮细胞上黏附分子、促炎细胞因子及所有类型HLA的表达显著更高,但心肌中单核细胞上的表达无增加。此外,与同一患者的骨骼肌相比,IRD患者的心肌显示出心脏微血管炎症和活化的局部表达显著更高。
心血管疾病患者心脏组织中黏附分子、HLA和促炎细胞因子的表达增加,表明涉及微血管和心肌细胞的局部炎症可能在心血管疾病的发病机制中起作用。与无IRD患者相比,IRD患者中更明显的变化可能导致IRD患者心血管疾病风险增加和过早死亡。