Expression of Rho Kinase and Its Mechanism in the Left Atrial Appendage in Patients with Atrial Fibrillation

Heart Surg Forum. 2018 Feb 19;21(1):E044-E048. doi: 10.1532/hsf.1851.

Abstract

To study the expression of Rho kinase (Rho associated coil forming protein kinase-1, ROCK-1) and its substrate myosin phosphatase target subunit 1 (myosin phosphatase target subunit-1, MYPT-1), connexin 40 (Cx40) and connexin 43 (Cx43) in the left atrial appendage of patients with atrial fibrillation, and explore the role of ROCK signaling pathway in patients with atrial fibrillation and its underlying mechanism. Methods: 40 patients undergoing open heart surgery were divided into two groups; atrial fibrillation group (AF group) and sinus rhythm group (SR group). About 100 mg of left atrial appendage tissue was taken during surgery and quickly frozen in liquid nitrogen. Immunohistochemistry and western blot were performed to evaluate the expression and location of ROCK-1, MYPT-1, Cx40 and Cx43 in the left atrial appendage tissue. Results: The results indicated that the expression of ROCK-1, MYPT-1, and Cx40 in the left atrial appendage in patients with atrial fibrillation was significantly upregulated (P < .01), the difference in the two groups was statistically significant, and ROCK-1, Cx40, and MYPT-1 expression in the AF group were higher than those in sinus rhythm group; there was a weakly positive expression of Cx43 protein in the AF group and sinus rhythm group, the difference was not statistically significant, and ROCK-1 and MYPT-1 expression showed a significant positive correlation (r = 0.968, P < .05), MYPT 1 and Cx40 protein expression was also positively correlated (r = 0.983, P < .05). Evidence in the left atrial appendage tissue of patients with atrial fibrillation showed that some proteins in Rho/ROCK pathway were upregulated, and MYPT-1 and Cx40 protein expression in AF group were significantly higher than that of SR group, which was also positively correlated; Cx43 showed a weak positive expression in both the SR group and AF group, which indicates that Rho kinase may induce expression of Cx40 by phosphorylation of MYPT-1; Cx43 may not be involved, suggesting that Rho kinase signaling pathway may activate and play an important role in the pathogenesis of atrial fibrillation lesions.

Keywords: Cx40; Cx43; LAA; MYPT-1; ROCK-1; atrial fibrillation.

MeSH terms

  • Adult
  • Aged
  • Atrial Appendage / enzymology*
  • Atrial Fibrillation / enzymology
  • Atrial Fibrillation / genetics*
  • Biomarkers / metabolism
  • Blotting, Western
  • Female
  • Gene Expression Regulation*
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • RNA / genetics*
  • Young Adult
  • rho-Associated Kinases / biosynthesis*

Substances

  • Biomarkers
  • RNA
  • rho-Associated Kinases