title: Enhanced expression of ROCK in left atrial myocytes of mitral regurgitation: a potential mechanism of myolysis.
abstract: 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.
authors.affiliation: 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. chc3@adm.cgmh.org.tw.
authors.forename: Huang-Chung
authors.initials: HC
authors.lastname: Chen
authors.affiliation: Division of Cardiovascular Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan. c9112772@ms25.hinet.net.
authors.forename: Jen-Ping
authors.initials: JP
authors.lastname: Chang
authors.affiliation: Graduate Institute of Biomedical Informatics, Taipei Medical University, Taipei, Taiwan. Kevinchang@tmu.edu.tw.
authors.forename: Tzu-Hao
authors.initials: TH
authors.lastname: Chang
authors.affiliation: Division of Cardiology, Chang Gung Memorial Hospital, Chiayi, Taiwan. dissertlin@yahoo.com.tw.
authors.forename: Yu-Sheng
authors.initials: YS
authors.lastname: Lin
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan. yaokuang@gmail.com.
authors.forename: Yao-Kuang
authors.initials: YK
authors.lastname: Huang
authors.affiliation: Division of Cardiology, Chang Gung Memorial Hospital, Chiayi, Taiwan. q12070@adm.cgmh.org.tw.
authors.forename: Kuo-Li
authors.initials: KL
authors.lastname: Pan
authors.affiliation: 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. cyfang@adm.cgmh.org.tw.
authors.forename: Chih-Yuan
authors.initials: CY
authors.lastname: Fang
authors.affiliation: 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. cjchen@adm.cgmh.org.tw.
authors.forename: Chien-Jen
authors.initials: CJ
authors.lastname: Chen
authors.affiliation: 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. erin05201982@yahoo.com.tw.
authors.forename: Wan-Chun
authors.initials: WC
authors.lastname: Ho
authors.affiliation: 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. chenmien@ms76.hinet.net.
authors.forename: Mien-Cheng
authors.initials: MC
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D053148:Caspase 3 / Q000378:metabolism*; D004789:Enzyme Activation; D005260:Female; D006325:Heart Atria / Q000201:enzymology / Q000473:pathology; D006801:Humans; D006984:Hypertrophy; D008297:Male; D008875:Middle Aged; D008944:Mitral Valve Insufficiency / Q000201:enzymology* / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000201:enzymology* / Q000473:pathology; D055815:Young Adult; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: C515851:ROCK1 protein, human; D054460:rho-Associated Kinases; D053148:Caspase 3