Core functional nodes and sex-specific pathways in human ischaemic and dilated cardiomyopathy

Area of Science:

• Cardiology
• Molecular Biology
• Biochemistry

Background:

• Studying human heart failure (HF) is limited by poor access to left ventricular myocardium.
• Ischaemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) are the most common causes of HF globally.

Purpose of the Study:

• To gain direct molecular insights into ICM and DCM using a human heart biobank.
• To identify proteomic and metabolomic differences in heart failure subtypes compared to controls.

Main Methods:

• Proteomic and metabolomic analyses were performed on 51 left ventricular (LV) samples from 44 cryopreserved human ICM and DCM hearts.
• Samples were compared to age-, gender-, and BMI-matched healthy donor controls.

Main Results:

• A significant reduction in serum amyloid A1 protein was observed in ICM hearts.
• Perturbed thyroid hormone signaling, reduced riboflavin-5-monophosphate, and fructose-6-phosphate were found in both ICM and DCM.
• Gender-specific alterations in arginine metabolism, mitochondrial substrates, and X chromosome-linked molecules were identified.

Conclusions:

• This research provides novel molecular insights into ICM and DCM using human heart tissue.
• The findings highlight potential gender-specific mechanisms in heart failure.
• An interactive online application offers a publicly available resource for further research.