Changes in microRNAs expression are involved in age-related atrial structural remodeling and atrial fibrillation

Abstract

Background Small noncoding microRNAs regulate gene expression in cardiac development and disease and have been implicated in the aging process and in the regulation of extracellular matrix proteins. However, their role in age-related cardiac remodeling and atrial fibrillation (AF) was not well understood. The present study was designed to decipher molecular mechanisms underlying age-related atrial structural remodeling and AF. Methods Three groups of dogs were studied: adult and aged dogs in sinus rhythm and with persistent AF induced by rapid atrial pacing. The expressions of microRNAs were measured by quantitative real-time polymerase chain reaction. Pathohistological and ultrastructural changes were tested by light and electron microscopy. Apoptosis index of myocytes was detected by TUNEL. Results Samples of atrial tissue showed the abnormal pathohistological and ultrastructural changes, the accelerated fibrosis, and apoptosis with aging and/or in AF dogs. Compared to the adult group, the expressions of microRNAs-21 and -29 were significantly increased, whereas the expressions of microRNAs-1 and -133 showed obvious downregulation tendency in the aged group. Compared to the aged group, the expressions of microRNAs-1, -21, and -29 was significantly increased in the old group in AF; contrastingly, the expressions of microRNA-133 showed obvious downregulation tendency. Conclusion These multiple aberrantly expressed microRNAs may be responsible for modulating the transition from adaptation to pathological atrial remodeling with aging and/or in AF.