Mechanical stretch induced interleukin-18 (IL-18) expression through Angiotensin subtype 1 receptor (AT1R) and endothelin-1 in cardiomyocytes.

Abstract Interleukin‐18 (IL‐18) is a proinflammatory cytokine with multiple biological functions. We and others have demonstrated that an increased level of circulating IL‐18 is one of the risk factors for cardiovascular diseases. Endothelin‐1 (ET‐1) has been reported to be a potent hypertrophy‐promoting factor through RhoA and Rho‐Kinase. Mechanical stretch induces a hypertrophic response, partly through the production of ET‐1 through Endothelin A receptor (ETAR). Moreover, it has also been reported that mechanical stretch induces cardiac hypertrophy through Angiotensin subtype 1 receptor (AT1R). However, the mechanism by which the IL‐18 gene expression is regulated in cardiomyocytes has not yet been fully understood. This study was designed to elucidate the functional significance of IL‐18 gene expression in response to mechanical stretch. Neonatal rat cardiomyocytes cultured on silicone dishes were subjected to stretch. The moderate 20% mechanical stretch resulted in the elevation of IL‐18 expression i...