Enhanced expression of ROCK in left atrial myocytes of mitral regurgitation: a potential mechanism of myolysis

二尖瓣反流左心房肌细胞中 ROCK 表达增强:肌溶解的潜在机制

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作者:Huang-Chung Chen, Jen-Ping Chang, Tzu-Hao Chang, Yu-Sheng Lin, Yao-Kuang Huang, Kuo-Li Pan, Chih-Yuan Fang, Chien-Jen Chen, Wan-Chun Ho, Mien-Cheng Chen

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.

Conclusions

The enhanced expression of ROCKs might be involved in the myolysis of the left atrial myocytes of MR patients.

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.

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