Cardiomyocyte Proteome Remodeling due to Isoproterenol-Induced Cardiac Hypertrophy during the Compensated Phase

Ricardo Cambraia Parreira, Diana Paola Gómez-Mendoza, Itamar Couto Guedes de Jesus, Rafael Pereira Lemos, Anderson Kennedy Santos, Cristiana Perdigão Rezende, Henrique César Pereira Figueiredo, Mauro Cunha Xavier Pinto, Frank Kjeldsen, Silvia Guatimosim, Rodrigo Ribeiro Resende, Thiago Verano-Braga*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

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.

Original languageEnglish
Article number2000017
JournalProteomics - Clinical Applications
Volume14
Issue number4
Number of pages12
ISSN1862-8346
DOIs
Publication statusPublished - Jul 2020

Keywords

  • cardiac hypertrophy
  • cardiomyocyte
  • isoproterenol
  • mass spectrometry
  • proteomics

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