LAUSR

Cardiac hypertrophy (CH) is a common risk factor for heart failure and even sudden cardiac death. Molecules have emerged as vital regulators in cardiac disorders. LIM domain kinase 1 (Limk1) is reported as a pro‐fibrotic mediator in patients with permanent atrial fibrillation and it has also been suggested to aggravate cardiac dysfunction in rats with chronic heart failure. The present study observed that Limk1 was significantly upregulated in the in vitro model of CH induced by angiotensin II (Ang‐II). Interestingly, silencing Limk1 led to inhibition of the hypertrophic phenotypes in Ang‐II‐treated cardiomyocytes. Next, through a series of mechanistic assays including RIP assay, RNA pull‐down assay, and luciferase reporter assay, miR‐93‐5p was verified to target Limk1. Furthermore, circ‐Zfp644 was validated as the sponge of miR‐93‐5p. Circ‐Zfp644 functioned as a ceRNA to upregulate Limk1 expression via sequestering miR‐93‐5p in Ang‐II‐treated cardiomyocytes. Finally, a range of rescue assays revealed that circ‐Zfp644 stimulated hypertrophic effects in Ang‐II‐treated cardiomyocytes via upregulating Limk1 while miR‐93‐5p exerted the opposite effects via its inhibition on Limk1. On the whole, the present study revealed that circ‐Zfp644 aggravated CH through modulating the miR‐93‐5p/Limk1 axis. The findings observed on the in vitro model of CH provided new potential for developing CH treatment.