Cardiovascular Research   2016 年 110 卷 2 期

2016.05.15

Aims Overexpression of either member of the miR-199 family, miR-199a-5p, or miR-199b-5p (hereinafter referred to as miR-199a or miR-199b) promotes pathological cardiac hypertrophy, but little is known about the role of endogenous miR-199 in cardiac development and disease. Our study aimed to determine the physiological function of the endogenous miR-199 family in cardiac homeostasis maintenance. Methods and results We generated a sponge transgenic mouse model with a specific disruption of miR-199 in the heart. To our surprise, we found that knockdown of endogenous miR-199 caused physiological cardiac hypertrophy characterized by an increased heart weight and cardiomyocyte size, but with normal cardiac morphology and function. Furthermore, we also identified PGC1?± as the target gene of the miR-199 family, and PGC1?± was also increased in sponge transgenic mice. Conclusion Inhibition of endogenous miR-199 led to physiological cardiac hypertrophy probably due to the up-regulation of PGC1?±, uncovering a surprising role for endogenous miR-199 in the maintenance of cardiac homeostasis.