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Proteome-wide Characterization and Pathophysiology Correlation in Non-ischemic Cardiomyopathies
Seonhwa Lee1, Dong-Gi Jang2,3, Yeon Ju Kyoung2,3
1Division of Cardiology, Department of Internal Medicine, Cardiovascular Center, Keimyung University Dongsan Hospital, Keimyung University School of Medicine, Daegu, Korea.
Insights
Advanced heart failure (HF) shows distinct proteomic differences based on cardiomyopathy etiology. Understanding these unique molecular pathways is key for developing targeted treatments for non-ischemic HF.
Area of Science:
- Cardiovascular Proteomics
- Molecular Pathophysiology
- Heart Failure Etiology
Background:
- Clinical outcomes in advanced heart failure (HF) can be similar across different cardiomyopathies.
- However, underlying proteomic differences related to pathophysiology exist.
- Identifying these proteomic variations is crucial for understanding disease mechanisms.
Purpose of the Study:
- To identify myocardial tissue-based proteomic characteristics.
- To elucidate the underlying molecular pathophysiology in non-ischemic cardiomyopathies of various etiologies.
Main Methods:
- Comparative proteomic analysis of myocardial tissue from non-ischemic cardiomyopathies (dilated cardiomyopathy [DCM], hypertrophic cardiomyopathy [HCM], myocarditis) and controls.
- Utilized tandem mass tags and liquid chromatography-mass spectrometry.
- Performed differential protein expression, Gene Ontology, and Ingenuity Pathway Analysis (IPA).
Main Results:
- Principal component analysis showed distinct clustering for controls, DCM, and HCM, with scattered myocarditis samples.
- DCM and HCM exhibited downregulated oxidative phosphorylation and upregulated sirtuin signaling.
- Myocarditis showed upregulated inflammatory pathways and downregulated Rho GDP dissociation inhibitors.
Conclusions:
- Non-ischemic cardiomyopathies in advanced HF display distinct proteomic expressions despite similar pathology.
- Tailored management strategies considering these proteomic differences warrant further investigation.
Background And Objectives:
Although the clinical consequences of advanced heart failure (HF) may be similar across different etiologies of cardiomyopathies, their proteomic expression may show substantial differences in relation to underlying pathophysiology. We aimed to identify myocardial tissue-based proteomic characteristics and the underlying molecular pathophysiology in non-ischemic cardiomyopathy with different etiologies.
Methods:
Comparative extensive proteomic analysis of the myocardium was performed in nine patients with biopsy-proven non-ischemic cardiomyopathies (3 dilated cardiomyopathy [DCM], 2 hypertrophic cardiomyopathy [HCM], and 4 myocarditis) as well as five controls using tandem mass tags combined with liquid chromatography-mass spectrometry. Differential protein expression analysis, Gene Ontology (GO) analysis, and Ingenuity Pathway Analysis (IPA) were performed to identify proteomic differences and molecular mechanisms in each cardiomyopathy type compared to the control. Proteomic characteristics were further evaluated in accordance with clinical and pathological findings.
Results:
The principal component analysis score plot showed that the controls, DCM, and HCM clustered well. However, myocarditis samples exhibited scattered distribution. IPA revealed the downregulation of oxidative phosphorylation and upregulation of the sirtuin signaling pathway in both DCM and HCM. Various inflammatory pathways were upregulated in myocarditis with the downregulation of Rho GDP dissociation inhibitors. The molecular pathophysiology identified by extensive proteomic analysis represented the clinical and pathological properties of each cardiomyopathy with abundant proteomes.
Conclusions:
Different etiologies of non-ischemic cardiomyopathies in advanced HF exhibit distinct proteomic expression despite shared pathologic findings. The benefit of tailored management strategies considering the different proteomic expressions in non-ischemic advanced HF requires further investigation.
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