Morphometric, Hemodynamic, and Multi-Omics Analyses in Heart Failure Rats with Preserved Ejection Fraction

Area of Science:

• Cardiology
• Molecular Biology
• Genomics

Background:

• Heart failure with preserved ejection fraction (HFpEF) lacks effective treatments due to complex risk factors.
• Understanding cellular and molecular changes in HFpEF is crucial for developing new therapies.

Purpose of the Study:

• To investigate molecular and cellular alterations in cardiomyocytes associated with HFpEF.
• To identify potential therapeutic targets for HFpEF.

Main Methods:

• Dahl salt-sensitive rats were fed a high-salt diet to induce HFpEF.
• Multi-omics analyses including shotgun proteomics, microarray, Western blot, and RT-PCR were employed.
• In vivo and ex vivo measurements confirmed HFpEF development and assessed cardiac function.

Main Results:

• HFpEF rats exhibited diastolic dysfunction, impaired systolic function, and prolonged myocyte repolarization.
• Multi-omics revealed significant differences between HFpEF and control groups, implicating pathways in muscle contraction, inflammation, and p53 signaling.
• Upregulation of Mff and Itga9, and downregulation of Map1lc3a, were linked to mitochondrial dysfunction, increased ROS, myocyte stiffness, and apoptosis.

Conclusions:

• Multi-omics analysis identified multiple pathways contributing to HFpEF.
• Mitochondrial fission, inflammation, and altered protein expression are key mechanisms in HFpEF pathogenesis.
• This research provides insights into HFpEF molecular mechanisms and suggests potential therapeutic targets.