Department of Geriatric Cardiology, Beijing Shijitan Hospital (affiliated to Capital Medical University), Beijing, China.
J Cell Biochem. 2019 Mar;120(3):2859-2868. doi: 10.1002/jcb.26575. Epub 2018 Dec 3.
To clarify the mechanism of heat shock protein 27 (HSP27) as a diagnostic biomarker in coronary heart disease (CHD) and atherosclerosis (AS).
Expressions of HSP27 in patients with CHD and healthy controls were determined by enzyme-linked immunosorbent assay and the expressions of HSP27 in aortas of patients with CHD and healthy controls were measured by immunohistochemistry. Receiver operating characteristic curve was applied to assess the diagnostic performance of HSP27 in CHD. ApoE mice were included and accordingly grouped. The expressions of HSP27 in AS plaque were measured by quantitative real-time polymerase chain reaction, immunohistochemistry, and Western blot analysis. AS plaque was observed using hematoxylin and eosin staining. DHE was used to detect reactive oxygen species (ROS) levels in aortas. The expressions of mitochondrial apoptosis-related proteins were measured by Western blot analysis. Cell apoptosis was determined by TUNEL staining.
HSP27 was highly expressed in patients with CHD than in healthy controls ( P < 0.01). In comparison to the normal group, the model group had increased the relative positive area of HSP27 and higher expressions of HSP27, Bax, caspase-3, and apoptosis index (AI) but decreased Bcl-2 expression in AS plaque, as well as larger plaque areas and elevated ROS levels in the aorta (all P < 0.05). The HSP27-small interfering RNA group had increased expressions of Bax, caspase-3, and AI but decreased Bcl-2 and HSP27 expressions in AS plaque, as well as larger plaque areas, the relative positive area of HSP27 and higher ROS levels in aorta when compared with those in the model group (all P < 0.05).
HSP27 exerts its protective role by suppressing ROS and AS progression by inhibiting mitochondria apoptosis pathway in CHD.
阐明热休克蛋白 27（HSP27）作为冠心病（CHD）和动脉粥样硬化（AS）诊断生物标志物的机制。
通过酶联免疫吸附试验测定 CHD 患者和健康对照者 HSP27 的表达，免疫组织化学法测定 CHD 患者和健康对照者主动脉 HSP27 的表达。应用受试者工作特征曲线评估 HSP27 对 CHD 的诊断性能。纳入载脂蛋白 E（ApoE）小鼠并进行相应分组。通过实时定量聚合酶链反应、免疫组织化学和 Western blot 分析测定 AS 斑块中 HSP27 的表达。用苏木精和伊红染色观察 AS 斑块。用二氢乙锭（DHE）检测主动脉中活性氧（ROS）水平。用 Western blot 分析测定线粒体凋亡相关蛋白的表达。用 TUNEL 染色法测定细胞凋亡。
与健康对照组相比，CHD 患者 HSP27 表达水平升高（P<0.01）。与正常组相比，模型组 AS 斑块中 HSP27、Bax、caspase-3 和凋亡指数（AI）的相对阳性面积及表达均升高，Bcl-2 表达降低，主动脉斑块面积增大，ROS 水平升高（均 P<0.05）。与模型组相比，HSP27-siRNA 组 AS 斑块中 Bax、caspase-3 和 AI 的表达升高，Bcl-2 和 HSP27 的表达降低，主动脉斑块面积、HSP27 相对阳性面积及 ROS 水平均升高（均 P<0.05）。
HSP27 通过抑制线粒体凋亡途径抑制 ROS 和 AS 进展，从而发挥对 CHD 的保护作用。
