二尖瓣反流患者左心房肌细胞中ROCK表达增强：一种潜在的肌溶解机制。
Enhanced expression of ROCK in left atrial myocytes of mitral regurgitation: a potential mechanism of myolysis.
作者信息
Chen Huang-Chung, Chang Jen-Ping, Chang Tzu-Hao, Lin Yu-Sheng, Huang Yao-Kuang, Pan Kuo-Li, Fang Chih-Yuan, Chen Chien-Jen, Ho Wan-Chun, Chen Mien-Cheng
机构信息
Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta Pei Road, Niao Sung District, Kaohsiung City, 83301, Taiwan.
Division of Cardiovascular Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
出版信息
BMC Cardiovasc Disord. 2015 May 9;15:33. doi: 10.1186/s12872-015-0038-9.
BACKGROUND
Severe mitral regurgitation (MR) may cause myolysis in the left atrial myocytes. Myolysis may contribute to atrial enlargement. However, the relationship between Rho-associated kinase (ROCK) and myolysis in the left atrial myocytes of MR patients remain unclear.
METHODS
This study comprised 22 patients with severe MR [12 with atrial fibrillation (AF) and ten in sinus rhythm]. Left atrial appendage tissues were obtained during surgery. Normal left atrial tissues were purchased. Immunofluorescence histochemical and immunoblotting studies were performed.
RESULTS
The expression of ROCK2 in the myolytic left atrial myocytes of MR AF patients (p = 0.009) and MR sinus patients (p = 0.011) were significantly higher than that of the normal subjects. Similarly, the expression of ROCK1 in the myolytic left atrial myocytes of MR AF patients was significantly higher than that of the normal subjects (p = 0.010), and the expression of ROCK1 in the myolytic left atrial myocytes of MR sinus patients was higher than that of the normal subjects (p = 0.091). Immunofluorescence study revealed significant co-localization and juxtaposition of ROCK2 and cleaved caspase-3 in the left atrial myocytes both in the MR AF group (Pearson's coefficient = 0.74 ± 0.03) and the MR sinus group (Pearson's coefficient = 0.73 ± 0.02). Similarly, immunofluorescence study revealed significant co-localization and juxtaposition of ROCK1 and cleaved caspase-3 in the left atrial myocytes both in the MR AF group (Pearson's coefficient = 0.65 ± 0.03) and the MR sinus group (Pearson's coefficient = 0.65 ± 0.03). Correlation analysis demonstrated that there was a significant direct relationship between the expression of ROCK2 in the myolytic left atrial myocytes and left atrial diameter in the MR patients (p = 0.041; r = 0.440). Moreover, the ratio of phosphorylated myosin-binding subunit of myosin light chain phosphatase (pMBS)/total MBS of left atrial tissues was significantly higher in the MR AF group (p < 0.04) and the MR sinus group (p < 0.04) compared with the normal control group.
CONCLUSIONS
The enhanced expression of ROCKs might be involved in the myolysis of the left atrial myocytes of MR patients.
背景
严重二尖瓣反流（MR）可能导致左心房肌细胞溶解。肌细胞溶解可能促使心房扩大。然而，Rho相关激酶（ROCK）与MR患者左心房肌细胞肌溶解之间的关系仍不清楚。
方法
本研究纳入22例严重MR患者[12例伴有心房颤动（AF），10例为窦性心律]。手术中获取左心耳组织。购买正常左心房组织。进行免疫荧光组织化学和免疫印迹研究。
结果
MR合并AF患者（p = 0.009）和MR窦性心律患者（p = 0.011）的肌溶解左心房肌细胞中ROCK2的表达显著高于正常受试者。同样，MR合并AF患者的肌溶解左心房肌细胞中ROCK1的表达显著高于正常受试者（p = 0.010），MR窦性心律患者的肌溶解左心房肌细胞中ROCK1的表达高于正常受试者（p = 0.091）。免疫荧光研究显示，在MR合并AF组（Pearson系数 = 0.74 ± 0.03）和MR窦性心律组（Pearson系数 = 0.73 ± 0.02）的左心房肌细胞中，ROCK2与裂解的半胱天冬酶-3均有显著的共定位和并列。同样，免疫荧光研究显示，在MR合并AF组（Pearson系数 = 0.65 ± 0.03）和MR窦性心律组（Pearson系数 = 0.65 ± 0.03）的左心房肌细胞中，ROCK1与裂解的半胱天冬酶-3均有显著的共定位和并列。相关性分析表明，MR患者肌溶解左心房肌细胞中ROCK2的表达与左心房直径之间存在显著的直接关系（p = 0.041；r = 0.440）。此外，与正常对照组相比，MR合并AF组（p < 0.04）和MR窦性心律组（p < 0.04）左心房组织中肌球蛋白轻链磷酸酶磷酸化肌球蛋白结合亚基（pMBS）/总MBS的比值显著更高。
结论
ROCKs表达增强可能参与了MR患者左心房肌细胞的肌溶解过程。
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