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. 2020 Jul;14(4):e2000017.
doi: 10.1002/prca.202000017. Epub 2020 Jun 23.

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

Ricardo Cambraia Parreira  1   2   3 , Diana Paola Gómez-Mendoza  1 , Itamar Couto Guedes de Jesus  1 , Rafael Pereira Lemos  1 , Anderson Kennedy Santos  1   2 , Cristiana Perdigão Rezende  4 , Henrique César Pereira Figueiredo  4 , Mauro Cunha Xavier Pinto  5 , Frank Kjeldsen  6 , Silvia Guatimosim  1 , Rodrigo Ribeiro Resende  2 , Thiago Verano-Braga  1
Affiliations

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

Ricardo Cambraia Parreira et al. Proteomics Clin Appl. 2020 Jul.

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.

Keywords: cardiac hypertrophy; cardiomyocyte; isoproterenol; mass spectrometry; proteomics.

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