Histone Deacetylase 7 protects against pathologic cardiac hypertrophy

Area of Science:

• Cardiovascular Biology
• Epigenetics
• Molecular Medicine

Background:

• Pathological cardiac hypertrophy precedes heart failure, but its transcriptional regulation is not fully understood.
• Class IIa histone deacetylases (HDACs) influence cardiac hypertrophy with complex effects, necessitating targeted therapies.
• The role of HDAC7 in cardiac stress response is unknown as it's not expressed in adult cardiomyocytes.

Purpose of the Study:

• To investigate the protective role of HDAC7 overexpression against pathological cardiac hypertrophy.
• To elucidate the molecular mechanisms underlying HDAC7's function in cardiac remodeling.

Main Methods:

• Utilized in vitro and in vivo molecular, biochemical, and physiological approaches.
• Assessed effects of HDAC7 overexpression on cardiomyocyte size and gene expression.
• Employed transverse aortic constriction model in vivo to evaluate cardiac function and remodeling.

Main Results:

• HDAC7 overexpression inhibited angiotensin II-induced cardiomyocyte enlargement and hypertrophic gene expression.
• In vivo, HDAC7 reduced cardiac hypertrophy, fibrosis, and functional decline post-transverse aortic constriction.
• HDAC7 directly repressed MEF2D target genes, and MEF2 binding was essential for its protective effects.

Conclusions:

• HDAC7 acts as a suppressor of pathological cardiac remodeling through a novel HDAC7-MEF2D pathway.
• HDAC7 represents a potential epigenetic target for preventing heart failure progression.
• HDAC7's distinct role among Class IIa HDACs offers new therapeutic avenues.