Multiple short-chain dehydrogenases/reductases are regulated in pathological cardiac hypertrophy

Area of Science:

• Cardiovascular Biology
• Molecular Genetics
• Biochemistry

Background:

• Cardiac hypertrophy (CH) is a significant risk factor for cardiovascular morbidity and mortality.
• Previous studies identified dysregulated short-chain dehydrogenase/reductase (SDR) genes in a rat model of CH.
• The SDR superfamily comprises enzymes crucial for various metabolic processes.

Purpose of the Study:

• To investigate the expression patterns of nine SDR genes in diverse CH models.
• To explore factors influencing the regulation of these SDR genes in the heart.
• To determine the sex-specific differences in SDR gene expression during CH.

Main Methods:

• Expression profiling of nine SDR genes in rat and mouse models of CH (aortic valve regurgitation, isoproterenol, angiotensin II infusion).
• In vitro studies using neonatal rat cardiomyocytes treated with phenylephrine (α1-adrenergic receptor agonist) and retinoic acid.
• Comparison of SDR gene expression in neonatal cardiomyocytes versus adult hearts.

Main Results:

• Eight out of nine studied SDR genes were down-regulated in various CH models, with a notable sex dimorphism favoring males.
• Phenylephrine treatment in cardiomyocytes mimicked the down-regulation observed in CH models.
• Retinoic acid treatment stimulated the expression of most SDR genes, suggesting a link to cardiomyocyte differentiation.

Conclusions:

• A specific group of SDR genes is modulated in animal models of CH, predominantly in males.
• The observed down-regulation of these genes in pathological CH may reflect the reactivation of a fetal gene expression program.
• These findings highlight potential sex-specific molecular mechanisms in cardiac hypertrophy.