Oriented responses of cultured cardiomyocytes by mechanical stretch is regulated by N-cadherin

Abstract

Objective: Hypertrophic cardiomyopathy (HCM) is a primary myocardial disease, leading to cardiac failure. Disarray of cardiomyocytes, characteristic of HCM, has been believed to lead to arrhythmia and weakness of contraction, though little is elucidated about the mechanisms for disarray. Interestingly, it was reported that mechanical stretch induced oriented responses of cardiomyocytes. To make clear the mechanisms for oriented responses, we investigated the functional significances of N-cadherin in cyclic stretch model. Methods: Neonatal rat cardiomyocytes cultured on silicone chambers were subjected to linear cyclic stretch. Mechanical stimulation was started at various times (3, 24, or 72h) after seeding and continued for 24h. Results: Three hours after cultivation, cardiomyocytes exhibited round-shape, attaching to the chamber, and stretch stimulation promoted cell orientation. In contrast, cells did not show oriented responses 72 hours after cultivation with the upregulation of its protein. Thus we replated the cardiomyocytes cultured for 72 hours and exposed the culture to stretch. The modulation of cell-cell adhesion by replating enabled cells to rearrange their orientation following stretch stimulation. Adenoviral gene transfer of dominant negative N-cadherin restored the ability to align in response to stretch. Conclusion: Our results suggested that N-cadherin could be a significant molecule as regulator of oriented responses of cardiomyocytes by mechanical stretch.