@article{10.1172/jci.insight.121541, author = {Lisa C. Green AND Sarah R. Anthony AND Samuel Slone AND Lindsey Lanzillotta AND Michelle L. Nieman AND Xiaoqing Wu AND Nathan Robbins AND Shannon M. Jones AND Sudeshna Roy AND A. Phillip Owens III AND Jeffrey Aube AND Liang Xu AND John N. Lorenz AND Burns C. Blaxall AND Jack Rubinstein AND Joshua B. Benoit AND Michael Tranter}, journal = {JCI Insight}, publisher = {The American Society for Clinical Investigation}, title = {Human antigen R as a therapeutic target in pathological cardiac hypertrophy}, year = {2019}, month = {2}, volume = {4}, url = {https://insight.jci.org/articles/view/121541}, abstract = {RNA binding proteins represent an emerging class of proteins with a role in cardiac dysfunction. We show that activation of the RNA binding protein human antigen R (HuR) is increased in the failing human heart. To determine the functional role of HuR in pathological cardiac hypertrophy, we created an inducible cardiomyocyte-specific HuR-deletion mouse and showed that HuR deletion reduces left ventricular hypertrophy, dilation, and fibrosis while preserving cardiac function in a transverse aortic constriction (TAC) model of pressure overload–induced hypertrophy. Assessment of HuR-dependent changes in global gene expression suggests that the mechanistic basis for this protection occurs through a reduction in fibrotic signaling, specifically through a reduction in TGF-β (Tgfb) expression. Finally, pharmacological inhibition of HuR at a clinically relevant time point following the initial development of pathological hypertrophy after TAC also yielded a significant reduction in pathological progression, as marked by a reduction in hypertrophy, dilation, and fibrosis and preserved function. In summary, this study demonstrates a functional role for HuR in the progression of pressure overload–induced cardiac hypertrophy and establishes HuR inhibition as a viable therapeutic approach for pathological cardiac hypertrophy and heart failure.}, number = {4}, doi = {10.1172/jci.insight.121541}, url = {https://doi.org/10.1172/jci.insight.121541}, }