BACKGROUND A heart attack occurs when coronary artery blockage interrupts the blood supply to the heart such as is seen in cardiovascular disease (CVD). Importantly, autophagy is commonly regarded as a host defense mechanism against microbial invaders. METHODS A total of 50 blood samples were obtained from cardiovascular (CV) patients in addition to 30 samples that were obtained from healthy individuals and served as controls. Macrophages were isolated in vitro and propagated from the blood samples. Autophagosome formation, cytokine secretion, and apolipoprotein B (ApoB) gene expression were monitored in patient samples and their derived macrophages. RESULTS The results showed that autophagy-related (Atg) LC3 and Atg5 genes were significantly down-regulated in all samples obtained from CV patients. Furthermore, the relative gene expression of ApoB, which plays the major role in lipoprotein metabolism, was significantly increased in CV patients. Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) levels were increased in these blood samples. Interestingly, targeting of ApoB by small interference RNA (siRNA) reduced the production levels of low-density lipoprotein (LDL), IL-6 and TNF-α in patient-derived macrophages. Further, treatment of patient-derived macrophages with rapamycin, an autophagy inducer agent, successfully regulated the production of LDL, IL-6, TNF-α, and ApoB expression via activation of autophagosome formation. CONCLUSION The current data reveal the potential disturbance of autophagy in CV patients that accompanied ApoB over-expression. Furthermore, our findings provide evidence for the protective role of autophagy in accumulation of pro-inflammatory cytokines and intracellular LDL degradation in CV patient-derived macrophages.

中文翻译：

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自噬体形成在心血管疾病中的中断，自噬保护反应的证据。

背景技术当冠状动脉阻塞中断向心脏的血液供应时发生心脏病发作，例如在心血管疾病（CVD）中所见。重要的是，自噬通常被视为抵抗微生物入侵者的宿主防御机制。方法除了从健康个体获得的30份样本作为对照外，还从心血管（CV）患者中获得了50份血液样本。巨噬细胞在体外分离并从血样中繁殖。在患者样品及其衍生的巨噬细胞中监测自噬体形成，细胞因子分泌和载脂蛋白B（ApoB）基因表达。结果结果显示，自CV患者获得的所有样品中，自噬相关（Atg）LC3和Atg5基因均显着下调。此外，在脂蛋白患者中，在脂蛋白代谢中起主要作用的ApoB的相对基因表达显着增加。这些血液样本中的白细胞介素6（IL-6）和肿瘤坏死因子-α（TNF-α）水平升高。有趣的是，通过小干扰RNA（siRNA）靶向ApoB降低了患者来源的巨噬细胞中低密度脂蛋白（LDL），IL-6和TNF-α的产生水平。此外，用雷帕霉素（一种自噬诱导剂）治疗患者来源的巨噬细胞，通过激活自噬体形成，成功调节了LDL，IL-6，TNF-α和ApoB表达的产生。结论当前的数据揭示了伴随ApoB过表达的CV患者自噬的潜在障碍。此外，