PMID- 29797568 OWN - NLM STAT- MEDLINE DCOM- 20190926 LR - 20211204 IS - 1097-4652 (Electronic) IS - 0021-9541 (Linking) VI - 233 IP - 11 DP - 2018 Nov TI - Excessive training induces molecular signs of pathologic cardiac hypertrophy. PG - 8850-8861 LID - 10.1002/jcp.26799 [doi] AB - Chronic exercise induces cardiac remodeling that promotes left ventricular hypertrophy and cardiac functional improvement, which are mediated by the mammalian or the mechanistic target of rapamycin (mTOR) as well as by the androgen and glucocorticoid receptors (GRs). However, pathological conditions (i.e., chronic heart failure, hypertension, and aortic stenosis, etc.) also induce cardiac hypertrophy, but with detrimental function, high levels of proinflammatory cytokines and myostatin, elevated fibrosis, reduced adenosine monophosphate-activated protein kinase (AMPK) activation, and fetal gene reactivation. Furthermore, recent studies have evidenced that excessive training induced an inflammatory status in the serum, muscle, hypothalamus, and liver, suggesting a pathological condition that could also be detrimental to cardiac tissue. Here, we verified the effects of three running overtraining (OT) models on the molecular parameters related to physiological and pathological cardiac hypertrophy. C57BL/6 mice performed three different OT protocols and were evaluated for molecular parameters related to physiological and pathological cardiac hypertrophy, including immunoblotting, reverse transcription polymerase chain reaction, histology, and immunohistochemistry analyses. In summary, the three OT protocols induced left ventricle (LV) hypertrophy with signs of cardiac fibrosis and negative morphological adaptations. These maladaptations were accompanied by reductions in AMPKalpha (Thr172) phosphorylation, androgen receptor, and GR expressions, as well as by an increase in interleukin-6 expression. Specifically, the downhill running-based OT model reduced the content of some proteins related to the mTOR signaling pathway and upregulated the beta-isoform of myosin heavy-chain gene expression, presenting signs of LV pathological hypertrophy development. CI - (c) 2018 Wiley Periodicals, Inc. FAU - da Rocha, Alisson L AU - da Rocha AL AD - Postgraduate Program in Rehabilitation and Functional Performance, Ribeirao Preto Medical School, University of Sao Paulo (USP), Ribeirao Preto, Sao Paulo, Brazil. FAU - Teixeira, Giovana R AU - Teixeira GR AD - Department of Physical Education, State University of Sao Paulo (UNESP), Presidente Prudente, Sao Paulo, Brazil. FAU - Pinto, Ana P AU - Pinto AP AD - Postgraduate Program in Rehabilitation and Functional Performance, Ribeirao Preto Medical School, University of Sao Paulo (USP), Ribeirao Preto, Sao Paulo, Brazil. FAU - de Morais, Gustavo P AU - de Morais GP AD - School of Physical Education and Sport of Ribeirao Preto, University of Sao Paulo (USP), Ribeirao Preto, Sao Paulo, Brazil. FAU - Oliveira, Luciana da C AU - Oliveira LDC AD - Postgraduate Program in Rehabilitation and Functional Performance, Ribeirao Preto Medical School, University of Sao Paulo (USP), Ribeirao Preto, Sao Paulo, Brazil. FAU - de Vicente, Larissa Gaioto AU - de Vicente LG AD - Postgraduate Program in Rehabilitation and Functional Performance, Ribeirao Preto Medical School, University of Sao Paulo (USP), Ribeirao Preto, Sao Paulo, Brazil. FAU - da Silva, Lilian E C M AU - da Silva LECM AD - Department of Ophthalmology, School of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil. FAU - Pauli, Jose R AU - Pauli JR AD - Laboratory of Molecular Biology of Exercise (LaBMEx), School of Applied Sciences, University of Campinas (UNICAMP), Campinas, Sao Paulo, Brazil. FAU - Cintra, Dennys E AU - Cintra DE AD - Laboratory of Molecular Biology of Exercise (LaBMEx), School of Applied Sciences, University of Campinas (UNICAMP), Campinas, Sao Paulo, Brazil. FAU - Ropelle, Eduardo R AU - Ropelle ER AD - Laboratory of Molecular Biology of Exercise (LaBMEx), School of Applied Sciences, University of Campinas (UNICAMP), Campinas, Sao Paulo, Brazil. FAU - de Moura, Leandro P AU - de Moura LP AD - Laboratory of Molecular Biology of Exercise (LaBMEx), School of Applied Sciences, University of Campinas (UNICAMP), Campinas, Sao Paulo, Brazil. FAU - Mekary, Rania A AU - Mekary RA AD - Department of Pharmaceutical Business and Administrative Sciences, MCPHS University, Boston, Massachusetts. AD - Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. FAU - de Freitas, Ellen C AU - de Freitas EC AD - School of Physical Education and Sport of Ribeirao Preto, University of Sao Paulo (USP), Ribeirao Preto, Sao Paulo, Brazil. FAU - da Silva, Adelino S R AU - da Silva ASR AUID- ORCID: 0000-0002-9679-8357 AD - Postgraduate Program in Rehabilitation and Functional Performance, Ribeirao Preto Medical School, University of Sao Paulo (USP), Ribeirao Preto, Sao Paulo, Brazil. AD - School of Physical Education and Sport of Ribeirao Preto, University of Sao Paulo (USP), Ribeirao Preto, Sao Paulo, Brazil. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180524 PL - United States TA - J Cell Physiol JT - Journal of cellular physiology JID - 0050222 RN - 0 (Interleukin-6) RN - 0 (Receptors, Androgen) RN - 0 (Receptors, Glucocorticoid) RN - EC 2.7.- (Protein Kinases) RN - EC 2.7.11.3 (AMP-Activated Protein Kinase Kinases) RN - EC 3.6.1.- (Nonmuscle Myosin Type IIB) RN - EC 3.6.1.- (nonmuscle myosin type IIB heavy chain) RN - EC 3.6.4.1 (Myosin Heavy Chains) SB - IM MH - AMP-Activated Protein Kinase Kinases MH - Animals MH - Cardiomegaly/blood/etiology/*genetics/physiopathology MH - Disease Models, Animal MH - Humans MH - Hypertrophy, Left Ventricular/blood/etiology/*genetics/physiopathology MH - Inflammation/*blood/etiology/genetics/physiopathology MH - Interleukin-6/genetics MH - Mice MH - Myosin Heavy Chains/genetics MH - Nonmuscle Myosin Type IIB/genetics MH - Physical Conditioning, Animal/*adverse effects MH - Protein Kinases/blood/genetics MH - Receptors, Androgen/genetics MH - Receptors, Glucocorticoid/genetics OTO - NOTNLM OT - collagen OT - excessive training OT - heart OT - mice OT - pathological hypertrophy EDAT- 2018/05/26 06:00 MHDA- 2019/09/27 06:00 CRDT- 2018/05/26 06:00 PHST- 2017/11/20 00:00 [received] PHST- 2018/04/30 00:00 [accepted] PHST- 2018/05/26 06:00 [pubmed] PHST- 2019/09/27 06:00 [medline] PHST- 2018/05/26 06:00 [entrez] AID - 10.1002/jcp.26799 [doi] PST - ppublish SO - J Cell Physiol. 2018 Nov;233(11):8850-8861. doi: 10.1002/jcp.26799. Epub 2018 May 24.