AUTHOR=Li Bin , Guo Yifan , Zhan Yongkun , Zhou Xinyan , Li Yongbo , Zhao Chao , Sun Ning , Xu Chen , Liang Qianqian 

TITLE=Cardiac Overexpression of XIN Prevents Dilated Cardiomyopathy Caused by TNNT2 ΔK210 Mutation

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.691749

DOI=10.3389/fcell.2021.691749

ISSN=2296-634X

ABSTRACT=<p><italic>TNNT2</italic> mutation is associated with a range of cardiac diseases, including dilated cardiomyopathy (DCM). However, the mechanisms underlying the development of DCM and heart failure remain incompletely understood. In the present study, we found the expression of cardiac XIN protein was reduced in <italic>TNNT2</italic>-ΔK210 hESCs-derived cardiomyocytes and mouse heart tissues. We further investigated whether XIN protects against <italic>TNNT2</italic> mutation-induced DCM. Overexpression of the repeat-containing isoform XINB decreased the percentage of myofilaments disorganization and increased cell contractility of <italic>TNNT2</italic>-ΔK210 cardiomyocytes. Moreover, overexpression of XINB by heart-specific delivery via AAV9 ameliorates DCM remodeling caused by <italic>TNNT2</italic>-ΔK210 mutation in mice, revealed by partially reversed cardiac dilation, systolic dysfunction and heart fibrosis. These results suggest that deficiency of XIN may play a critical role in the development of DCM. Consequently, our findings may provide a new mechanistic insight and represent a therapeutic target for the treatment of idiopathic DCM.</p>