Metabolic Acidosis Results in Sexually Dimorphic Response in the Heart Tissue

Area of Science:

• Cardiovascular Physiology
• Metabolic Disorders
• Transcriptomics

Background:

• Metabolic acidosis (MA) is a prevalent blood pH imbalance affecting the heart.
• The heart's limited regeneration and high metabolic rate make it susceptible to chronic low-grade MA.
• Understanding MA's cardiac effects is crucial for managing associated health risks.

Purpose of the Study:

• To systematically investigate the cardiac effects of low-grade metabolic acidosis.
• To identify gender-based differences in MA-induced cardiovascular gene expression.
• To establish a systems-level understanding of MA's impact on cardiovascular tissue.

Main Methods:

• Male and female mice were treated with ammonium chloride (NH4Cl) for two weeks to induce low-grade MA.
• Blood chemistry was analyzed to confirm MA and assess physiological compensation.
• Cardiac tissue transcriptomic analysis was performed to identify gene expression changes.

Main Results:

• Low-grade MA was confirmed by reduced blood pH and bicarbonate levels with minimal respiratory compensation.
• Significant gender-based differences were observed in cardiac gene expression profiles.
• Males showed alterations in genes linked to dilated cardiomyopathy, while females exhibited changes in cardiac contractility and Na/K/ATPase-Src signaling.

Conclusions:

• Low-grade MA induces distinct cardiovascular transcriptomic changes in male and female mice.
• These findings highlight sex differences in MA-related cardiac damage.
• The study provides a foundation for developing targeted interventions to mitigate MA-induced cardiovascular pathology.