Left ventricular myocardial molecular profile of human diabetic ischaemic cardiomyopathy

Area of Science:

• Cardiovascular Science
• Metabolomics
• Molecular Biology

Background:

• Ischaemic cardiomyopathy is a leading cause of heart failure.
• Diabetes mellitus frequently coexists with ischaemic cardiomyopathy, worsening patient prognosis.
• The combined molecular effects of these conditions are poorly understood.

Purpose of the Study:

• To elucidate the molecular signature of ischaemic cardiomyopathy in the presence of diabetes.
• To investigate the interplay between diabetes and ischaemic cardiomyopathy at a multi-omic level.

Main Methods:

• Multi-omic analyses (proteomics, metabolomics) were performed on human left ventricular myocardium.
• Samples included patients with ischaemic cardiomyopathy, non-ischaemic cardiomyopathy, diabetes, and healthy controls.
• Tissue was obtained from pre-mortem human subjects.

Main Results:

• Downregulation of fatty acid transport and oxidation proteins was prominent in ischaemic cardiomyopathy with diabetes.
• Despite some protein downregulation, acylcarnitines and certain metabolic pathways suggested incomplete lipid metabolism impairment.
• Exacerbated oxidative phosphorylation, oxidative stress, myofibrosis, and cardiomyocyte cytoarchitecture changes were observed, particularly in the combined condition.

Conclusions:

• Diabetes significantly alters the pathological phenotype of ischaemic cardiomyopathy.
• Lipid metabolism in heart failure with diabetes presents a complex picture requiring a re-evaluation.
• Understanding these molecular interactions is crucial for developing targeted therapies for heart failure patients with diabetes.