TY - JOUR
T1 - Cardiomyocyte Proteome Remodeling due to Isoproterenol-Induced Cardiac Hypertrophy during the Compensated Phase
AU - Parreira, Ricardo Cambraia
AU - Gómez-Mendoza, Diana Paola
AU - de Jesus, Itamar Couto Guedes
AU - Lemos, Rafael Pereira
AU - Santos, Anderson Kennedy
AU - Rezende, Cristiana Perdigão
AU - Figueiredo, Henrique César Pereira
AU - Pinto, Mauro Cunha Xavier
AU - Kjeldsen, Frank
AU - Guatimosim, Silvia
AU - Resende, Rodrigo Ribeiro
AU - Verano-Braga, Thiago
N1 - This article is protected by copyright. All rights reserved.
PY - 2020/7
Y1 - 2020/7
N2 - 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.
AB - 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.
KW - cardiac hypertrophy
KW - cardiomyocyte
KW - isoproterenol
KW - mass spectrometry
KW - proteomics
U2 - 10.1002/prca.202000017
DO - 10.1002/prca.202000017
M3 - Journal article
C2 - 32506788
SN - 1862-8346
VL - 14
JO - Proteomics - Clinical Applications
JF - Proteomics - Clinical Applications
IS - 4
M1 - 2000017
ER -