Key result
Proteomic profiling of mouse models revealed 286 differentially expressed proteins, showing that while oxidative phosphorylation and metabolism are altered in both ischemic and dilated cardiomyopathy, significant heterogeneity exists between them.
Why the study?
Heart failure causes high morbidity and mortality, and understanding differing pathophysiological mechanisms will contribute to prevention and individualized therapy.
Does the cardiac proteome profile differ between ischemic and dilated cardiomyopathy mouse models?
Does the cardiac proteome profile differ between ischemic and dilated cardiomyopathy mouse models?
Ischemic and dilated cardiomyopathy mouse models exhibit distinct cardiac proteomic profiles, particularly in metabolic and AMPK signaling pathways, highlighting the pathophysiological heterogeneity of heart failure.
Distinct proteomes in ischemic versus dilated cardiomyopathy models caution against uniform HF strategies; extends metabolic heterogeneity data but leaves open human translation.
Heart failure (HF) is a worldwide pandemic with an unacceptable high level of morbidity and mortality. Understanding the different pathophysiological mechanisms will contribute to prevention and individualized therapy of HF. We established mouse models for ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) by inducing myocardial infarction (MI) and Coxsackievirus B3 infection, respectively. Isobaric tags for relative and absolute quantitation and liquid chromatography coupled with tandem mass spectrometry technology was used to identify the protein expression profiles in control and failing hearts. A total of 1,638 proteins were identified and compared in this proteomics analysis. Among them, 286 proteins were differently expressed. Gene ontology, KEGG pathway and ingenuity pathway analysis was performed to systematically assess the potential connections of the differentially expressed proteins to biological functions. Compared with control group, the differentially expressed proteins derived from the hearts of ICM and DCM mice were partially similar and mainly modulated in oxidative phosphorylation, metabolism and protein folding pathways. Moreover, difference still existed, the differentially expressed proteins between DCM and ICM hearts were significantly modulated in oxidative phosphorylation, metabolic and AMPK signaling pathways. Confirmatory western bolt analysis demonstrated that SDHB was down-regulated in both ICM and DCM hearts, while UQCRQ, GLUT4 and adiponectin were up-regulated in ICM hearts. Adenosine triphosphate (ATP) concentration significantly decreased in both DCM and ICM hearts. The protein expression of phospho-AMPKα decreased significantly in DCM hearts, but increased in ICM. In summary, oxidative phosphorylation, cardiac metabolism, and protein folding play critical roles in the pathogenesis of HF. The diverse changes in protein expression profiles between failing hearts induced by either MI or CVB3 infection demonstrated the heterogeneity of HF. Understanding the differences in proteome profiles could offer more precise therapeutic options for HF.
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Lu et al. (2019) studied Ischemic and Dilated Cardiomyopathy (n=30). Myocardial infarction or Coxsackievirus B3 infection vs. Sham-surgery and saline injection was evaluated on Differentially expressed proteins. Proteomic profiling of mouse models revealed 286 differentially expressed proteins, showing that while oxidative phosphorylation and metabolism are altered in both ischemic and dilated cardiomyopathy, significant heterogeneity exists between them.
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