Isoform-Specific Divergent Roles of Class I HDACs in Cardiac Hypertrophic Remodeling
DOI:
https://doi.org/10.54097/176fb211Keywords:
cardiac hypertrophy, Class I HDAC, knockdown, siRNA.Abstract
Class I histone deacetylases are emerging targets to manage cardiac hypertrophy. To delineate their individual roles, we used siRNA to knock down each HDAC isoform in human AC16 cardiomyocytes, in the presence or absence of angiotensin II (AngII). We found that HDAC1 and HDAC3 silencing could effectively reduce MYH7 expression and partially reverse cellular enlargement, whereas HDAC2 knockdown surprisingly exacerbated hypertrophy. Cross-isoform compensatory effects were also observed. RNA sequencing revealed distinct gene regulation profiles driven by different HDAC inhibitions. These results suggest that Class I HDAC isoforms mediate distinct, sometimes opposing, effects on cardiac hypertrophy.
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