Cellular stress response plays an important role in the pathophysiology of coronary artery disease (CAD). Inhibition of cellular stress may provide a novel clinical approach regarding the diagnosis and treatment of CAD. Fibroblasts constitute 60-70% of cardiac cells and have a crucial role in cardiovascular function. Hence, the aim of this study was to show a potential therapeutic application of proteins derived from heat-stressed fibroblast in CAD patients. Fibroblasts were isolated from the foreskin and cultured under heat stress conditions. Surprisingly, 1.06% of the cells exhibited a necrotic death pattern. Furthermore, heat-stressed fibroblasts produced higher level of total proteins than control cells. In SDS-PAGE analysis, a 70 kDa protein band was observed in stressed cell culture supernatants which appeared as two acidic spots with close pI in the two-dimensional electrophoresis. To evaluate the immunogenic properties of fibroblast-derived heat shock proteins (HSPs), the serum immunoglobulin-G (IgG) was measured by ELISA in 50 CAD patients and 50 normal subjects who had been diagnosed through angiography. Interestingly, the level of anti-HSP antibody was significantly higher in non-CAD individuals in comparison with the patient’s group (). The odds ratio for CAD was 5.06 () in cut-off value of 30 AU/mL of anti-HSP antibody. Moreover, ROC analysis showed that anti-HSP antibodies had a specificity of 74% and a sensitivity of 64%, which is almost equal to 66% sensitivity of exercise stress test (EST) as a CAD diagnostic method. These data revealed that fibroblast-derived HSPs are suitable for the diagnosis and management of CAD through antibody production.

中文翻译：

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与正常受试者相比，冠状动脉疾病患者对热应激成纤维细胞衍生蛋白的抗体水平较低

细胞应激反应在冠状动脉疾病 (CAD) 的病理生理学中起重要作用。细胞应激的抑制可能为 CAD 的诊断和治疗提供一种新的临床方法。成纤维细胞占心脏细胞的 60-70%，在心血管功能中起着至关重要的作用。因此，本研究的目的是展示来自热应激成纤维细胞的蛋白质在 CAD 患者中的潜在治疗应用。从包皮中分离成纤维细胞并在热应激条件下培养。令人惊讶的是，1.06% 的细胞表现出坏死性死亡模式。此外，热应激的成纤维细胞比对照细胞产生更高水平的总蛋白质。在 SDS-PAGE 分析中，在受压的细胞培养上清液中观察到 70 kDa 的蛋白质条带，在二维电泳中​​表现为两个具有接近 pI 的酸性点。为了评估成纤维细胞衍生的热休克蛋白 (HSP) 的免疫原性，通过 ELISA 在 50 名 CAD 患者和 50 名通过血管造影确诊的正常受试者中测量了血清免疫球蛋白 G (IgG)。有趣的是，与患者组相比，非 CAD 个体的抗 HSP 抗体水平显着更高。）。CAD 的优势比为 5.06 ()的截止值为 30 AU/mL 的抗 HSP 抗体。此外，ROC分析表明，抗HSP抗体的特异性为74%，敏感性为64%，几乎与作为CAD诊断方法的运动负荷试验（EST）的敏感性66%相当。这些数据表明，成纤维细胞来源的 HSP 适合通过抗体产生诊断和管理 CAD。