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Published on: May 25, 2022
Cardiomyocyte Proteome Remodeling due to Isoproterenol-Induced Cardiac Hypertrophy during the Compensated Phase
Ricardo Cambraia Parreira1,2,3, Diana Paola Gómez-Mendoza1, Itamar Couto Guedes de Jesus1
1Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, 31270-901, Brazil.
Insights
This study reveals molecular changes in early cardiac hypertrophy using proteomic analysis. Identified markers like MYH7 may aid in early diagnosis of heart failure.
Area of Science:
- Cardiovascular Biology
- Proteomics
- Molecular Cardiology
Background:
- Cardiac hypertrophy is a significant risk factor for heart failure.
- Early molecular events in compensated cardiac hypertrophy remain incompletely understood.
Purpose of the Study:
- To comprehensively characterize molecular events in early compensated cardiac hypertrophy at the cardiomyocyte level.
- To identify potential early diagnostic markers for cardiac hypertrophy.
Main Methods:
- Quantitative label-free proteomic analysis of cardiomyocytes.
- Isoproterenol (ISO) treatment in mice to induce hypertrophy.
- Canonical pathway analysis and confocal microscopy.
Main Results:
- Isoproterenol-induced hypertrophy activates actin cytoskeleton and integrin-linked kinase (ILK) signaling, while inhibiting sirtuin signaling.
- Upregulation of myosin-7 (MYH7) impacts cardiac contractile and calcium signaling.
- Identified potential early markers: APBB1, GOLGA4, HOOK1, KATNA1, KIFBP, MAN2B2, and SLC16A1.
Conclusions:
- Provides a molecular map of ISO-induced compensated cardiac hypertrophy in cardiomyocytes.
- Identified marker candidates may facilitate early diagnosis and intervention for cardiac hypertrophy and heart failure.
Purpose:
Although the pathophysiological response of cardiac tissue to pro-hypertrophic stimulus is well characterized, a comprehensive characterization of the molecular events underlying the pathological hypertrophy in cardiomyocytes during the early compensated cardiac hypertrophy is currently lacking.
Experimental Design:
A quantitative label-free proteomic analysis of cardiomyocytes isolated was conducted from mice treated subcutaneously with isoproterenol (ISO) during 7 days in comparison with cardiomyocytes from control animals (CT).
Results:
Canonical pathway analysis of dysregulated proteins indicated that ISO-hypertrophy drives the activation of actin cytoskeleton and integrin-linked kinase (ILK) signaling, and inhibition of the sirtuin signaling. Alteration in cardiac contractile function and calcium signaling are predicted as downstream effects of ISO-hypertrophy probably due to the upregulation of key elements such as myosin-7 (MYH7). Confocal microscopy corroborated that indeed ISO-treatment led to increased abundance of MYH7. Potential early markers for cardiac hypertrophy as APBB1, GOLGA4, HOOK1, KATNA1, KIFBP, MAN2B2, and SLC16A1 are also reported.
Conclusions And Clinical Relevance:
The data consist in a complete molecular mapping of ISO-induced compensated cardiac hypertrophy model at cardiomyocyte level. Marker candidates reported may assist early diagnosis of cardiac hypertrophy and ultimately heart failure.
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