Our data suggest that cardiac TH action includes a novel level of regulation in which a unique set of TH-dependent miRNAs primarily suppresses pathological hypertrophic signaling. The predicted regulation of 19% of these targets indicates enhancement of physiological hypertrophy, while 56% indicates suppression of pathological remodeling. A total of 27 mRNAs were identified as bona fide targets. The analysis was further restricted to proteins that have been validated as key factors in hypertrophic signal transduction in mouse models of ventricular remodeling. T3 treatment increased LV weight by 38% ( p 2-fold change ( p < 0.05) were included in Ingenuity Pathway Analysis to predict target mRNAs involved in cardiac hypertrophy. C57Bl/6J mice were rendered hypothyroid by treatment with propylthiouracil and were subsequently treated for 3 days with TH (T3) or saline. Because little is known about the involvement of miRNAs in cardiac TH action and hypertrophy, we examined the miRNA expression profile of the hypertrophied left ventricle (LV) using a mouse model of TH-induced cardiac hypertrophy. MicroRNAs (miRNAs) are important modulators of signal-transduction pathways driving adverse remodeling.

Normal cardiac function is maintained in this form of hypertrophy, whereas progressive contractile dysfunction is a hallmark of pathological hypertrophy.

Higher levels of TH induce ventricular hypertrophy, primarily in response to an increase in hemodynamic load.

Department of Physiology, VU University Medical Center, Institute for Cardiovascular Research, Amsterdam, NetherlandsĬardiomyocyte size in the healthy heart is in part determined by the level of circulating thyroid hormone (TH).

Pathological hypertrophy examples