Assessment of left ventricular tissue mitochondrial bioenergetics in patients with stable coronary artery disease

Area of Science:

• Cardiology
• Molecular Biology
• Biochemistry

Background:

• Recurrent myocardial ischemia in coronary artery disease (CAD) can impair left ventricular (LV) function.
• Understanding chronic metabolic and transcriptomic changes in the LV myocardium is crucial for managing CAD patients.

Purpose of the Study:

• To investigate global and regional metabolomic and transcriptomic adaptations in the LV myocardium of CAD patients.
• To compare these adaptations to healthy donor hearts and assess differences between ischemic and non-ischemic regions.

Main Methods:

• Observational cohort study involving 33 CAD patients undergoing coronary artery bypass grafting.
• Acquisition of paired transmural LV biopsies from ischemic and non-ischemic regions.
• Analysis of adenosine triphosphate (ATP):adenosine diphosphate (ADP) ratio, gene expression (oxidative phosphorylation - OXPHOS), and metabolite profiles.
• Comparison with LV samples from 11 donor hearts.

Main Results:

• CAD patients exhibited a reduced global myocardial ATP:ADP ratio compared to donors.
• Increased expression of OXPHOS genes was observed across multiple cell types in CAD patients.
• No significant regional differences in ATP:ADP ratio or OXPHOS gene expression were found between ischemic and non-ischemic LV segments.
• Dysregulation of metabolites, including succinate, was noted in patients with reduced LV ejection fraction.

Conclusions:

• Viable myocardium in stable CAD demonstrates global bioenergetic and transcriptional alterations.
• These changes occur systemically within the LV, irrespective of regional inducible ischemia.
• Findings highlight chronic adaptations in heart metabolism and gene expression in response to CAD.