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Investigating Cardiac Metabolism in the Isolated Perfused Mouse Heart with Hyperpolarized [1-13C]Pyruvate and 13C/31P NMR Spectroscopy
Published on: April 21, 2023
The Correlation of PPARα Activity and Cardiomyocyte Metabolism and Structure in Idiopathic Dilated Cardiomyopathy
E Czarnowska1, D Domal-Kwiatkowska2, E Reichman-Warmusz3
1Department of Pathology, The Children's Memorial Health Institute, Aleja Dzieci Polskich 20, 04-730 Warsaw, Poland.
Insights
Elevated PPARα in heart failure (HF) correlates with adverse metabolic and structural changes. This suggests a narrow therapeutic window for interventions targeting cardiac metabolism and cardiomyocyte structure in failing hearts.
Area of Science:
- Cardiology
- Molecular Biology
- Biochemistry
Background:
- Heart failure (HF) progression involves complex metabolic and structural changes in cardiomyocytes.
- Peroxisome proliferator-activated receptor alpha (PPARα) plays a role in cardiac metabolism, but its precise relationship with HF progression and structural remodeling is not fully understood.
Purpose of the Study:
- To investigate the relationship between PPARα expression and metabolic-structural characteristics during the progression of heart failure in dilated cardiomyopathy (DCM) patients.
- To determine the correlation between PPARα levels and left ventricular ejection fraction (LVEF) and identify potential therapeutic windows.
Main Methods:
- Analysis of endomyocardial biopsy samples from HF patients grouped by LVEF (45-50%, 30-40%, <30%) and healthy controls (>60%).
- Quantification of mRNA expression for PPARα, fatty acid translocase/CD36 (FAT/CD36), carnitine palmitoyltransferase-1 (CPT-1), glucose transporter-4 (GLUT-4), and pyruvate dehydrogenase kinase-4 (PDK-4).
- Assessment of cardiomyocyte structural changes and glycogen accumulation.
Main Results:
- PPARα mRNA expression was low in early HF (LVEF 45-50%), high in moderate HF (LVEF 30-40%), and similar to controls in advanced HF (LVEF <30%).
- FAT/CD36 and CPT-1 mRNA levels mirrored PPARα changes, while GLUT-4 and PDK-4 mRNA were continuously overexpressed in moderate to advanced HF.
- Increased PPARα expression correlated with cardiomyocyte structural changes, glycogen accumulation, and a negative correlation with LVEF.
Conclusions:
- Elevated PPARα levels may directly contribute to adverse metabolic and structural remodeling in the failing heart.
- There is a limited therapeutic window for interventions aimed at modulating cardiac metabolism and protecting cardiomyocyte structure in HF.
- Understanding the dynamic role of PPARα in HF progression is crucial for developing targeted therapies.
Abstract:
This study aimed to define relationship between PPARα expression and metabolic-structural characteristics during HF progression in hearts with DCM phenotype. Tissue endomyocardial biopsy samples divided into three groups according to LVEF ((I) 45-50%, n = 10; (II) 30-40%, n = 15; (III) <30%, n = 15; and control (donor hearts, >60%, n = 6)) were investigated. The PPARα mRNA expression in the failing hearts was low in Group (I), high in Group (II), and comparable to that of the control in Group (III). There were analogous changes in the expression of FAT/CD36 and CPT-1 mRNA in contrast to continuous overexpression of GLUT-4 mRNA and significant increase of PDK-4 mRNA in Group (II). In addition, significant structural changes of cardiomyocytes with glycogen accumulation were accompanied by increased expression of PPARα. For the entire study population with HF levels of FAT/CD36 mRNA showed a strong tendency of negative correlation with LVEF. In conclusion, PPARα elevated levels may be a direct cause of adverse remodeling, both metabolic and structural. Thus, there is limited time window for therapy modulating cardiac metabolism and protecting cardiomyocyte structure in failing heart.
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Cardiomyopathy II: Dilated Cardiomyopathy
Cardiomyopathy IV: Restrictive Cardiomyopathy
Cardiomyopathy I: Introduction and Classification
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Cardiomyopathy III: Hypertrophic Cardiomyopathy

