Catestatin Protects Against Diastolic Dysfunction by Attenuating Mitochondrial Reactive Oxygen Species Generation

Area of Science:

• Cardiology
• Molecular Biology
• Mitochondrial Medicine

Background:

• Catestatin is a cardioprotective peptide with potential roles in cardiovascular diseases.
• Heart failure with preserved ejection fraction (HFpEF) presents complex pathophysiology, particularly diastolic dysfunction.
• The specific mechanisms of catestatin in HFpEF remain to be fully elucidated.

Purpose of the Study:

• To investigate the therapeutic role of catestatin in a mouse model of HFpEF with diastolic dysfunction.
• To explore the impact of catestatin on mitochondrial function and oxidative stress in HFpEF.
• To assess serum catestatin levels in HFpEF patients and their correlation with disease parameters.

Main Methods:

• Utilized a mouse model of HFpEF induced by transverse aortic constriction and deoxycorticosterone acetate pellet implantation.
• Administered recombinant catestatin and assessed cardiac function using Doppler tissue imaging and pressure-volume loop catheterization.
• Performed transcriptomic analysis, mitochondrial assays (respiratory chain components, proton leak, ROS generation), and measured serum catestatin concentrations in patients.

Main Results:

• Catestatin treatment improved diastolic dysfunction and reduced left ventricular stiffness, cardiac hypertrophy, and myocardial fibrosis in HFpEF mice.
• Catestatin downregulated mitochondrial electron transport chain components, reversed mitochondrial abnormalities, and decreased ROS generation.
• Serum catestatin levels were elevated in HFpEF patients and correlated positively with the E/e' ratio, suggesting a compensatory mechanism.

Conclusions:

• Catestatin demonstrates protective effects against diastolic dysfunction in HFpEF by mitigating mitochondrial electron transport chain-derived ROS.
• Elevated serum catestatin in HFpEF patients may represent an insufficient, self-compensatory response to the condition.