Chen Song-Ming, Li Yu-Guang, Wang Dong-Ming, Zhang Guo-Hong, Tan Chun-Jiang
Department of Cardiology, the First Affiliated Hospital, Medical College, Shantou University, Shantou Guangdong, China.
Clin Chem Lab Med. 2009;47(3):327-33. doi: 10.1515/CCLM.2009.073.
The increased expression of heme oxygenase-1 content, a stress-response protein, directly correlates with the incidence of coronary heart disease. Down-regulation of hypoxia inducible factor-1alpha activity, a major downstream effector of the signaling pathways activated by hypoxia, increases cell survival after hypoxia. The ubiquitin system, a non-lysosomal pathway of protein degradation, is involved in processes of coronary heart disease. The aim of this study was to investigate the expression of heme oxygenase-1, hypoxia inducible factor-1alpha, and ubiquitin in both monocytes and lymphocytes isolated from patients at the mRNA and protein levels in different stages of coronary heart disease and their possible correlation.
A total of 90 patients with coronary heart disease (30 acute myocardial infarction, 30 unstable angina pectoris, and 30 stable angina pectoris) were selected, and 30 cases with normal coronary artery served as controls. The mRNA and protein expression of heme oxygenase-1, hypoxia inducible factor-1alpha, and ubiquitin in monocytes and lymphocytes were examined by semi-quantitative reverse transcriptase polymerase chain reaction and Western blotting, respectively.
The mRNA expression of heme oxygenase-1 and ubiquitin was associated with the severity of coronary heart disease (p<0.05). There was no significant difference in hypoxia inducible factor-1alpha mRNA expression between the coronary heart disease patients and controls. The protein expression of heme oxygenase-1, hypoxia inducible factor-1alpha, and ubiquitin was significantly stronger in patients with coronary heart disease than in controls, and the expression levels increased with the severity of the disease. There was a positive association between heme oxygenase-1 and hypoxia inducible factor-1alpha and ubiquitin, antioxidative therapy with adrenergic receptor blocker, angiotensin-converting enzyme inhibitor or statins up-regulated the expression of heme oxygenase-1 and hypoxia inducible factor-1alpha.
These data suggest that heme oxygenase-1, hypoxia inducible factor-1alpha, and ubiquitin are involved in the development and progression of coronary heart disease and thus may be useful biomarkers for coronary heart disease.
血红素加氧酶-1含量作为一种应激反应蛋白，其表达增加与冠心病的发病率直接相关。缺氧诱导因子-1α活性的下调是缺氧激活的信号通路的主要下游效应器，可增加缺氧后的细胞存活率。泛素系统作为蛋白质降解的非溶酶体途径，参与冠心病的发病过程。本研究旨在探讨血红素加氧酶-1、缺氧诱导因子-1α和泛素在冠心病患者不同阶段分离的单核细胞和淋巴细胞中的mRNA和蛋白质水平表达及其可能的相关性。
选取90例冠心病患者（30例急性心肌梗死、30例不稳定型心绞痛和30例稳定型心绞痛），并选取30例冠状动脉正常者作为对照。分别采用半定量逆转录聚合酶链反应和蛋白质印迹法检测单核细胞和淋巴细胞中血红素加氧酶-1、缺氧诱导因子-1α和泛素的mRNA和蛋白质表达。
血红素加氧酶-1和泛素的mRNA表达与冠心病的严重程度相关（p<0.05）。冠心病患者与对照组之间缺氧诱导因子-1α mRNA表达无显著差异。冠心病患者血红素加氧酶-1、缺氧诱导因子-1α和泛素的蛋白表达明显强于对照组，且表达水平随疾病严重程度增加。血红素加氧酶-1与缺氧诱导因子-1α和泛素之间呈正相关，使用肾上腺素能受体阻滞剂、血管紧张素转换酶抑制剂或他汀类药物进行抗氧化治疗可上调血红素加氧酶-1和缺氧诱导因子-1α的表达。
这些数据表明，血红素加氧酶-１、缺氧诱导因子-1α和泛素参与冠心病的发生发展，因此可能是冠心病有用的生物标志物。
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