Excessive training induces molecular signs of pathologic cardiac hypertrophy

Author(s):Show less -

da Rocha, Alisson L. ^[1] ; Teixeira, Giovana R. ^[2] ; Pinto, Ana P. ^[1] ; de Morais, Gustavo P. ^[3] ; Oliveira, Luciana da C. ^[1] ; de Vicente, Larissa Gaioto ^[1] ; da Silva, Lilian E. C. M. ^[4] ; Pauli, Jose R. ^[5] ; Cintra, Dennys E. ^[5] ; Ropelle, Eduardo R. ^[5] ; de Moura, Leandro P. ^[5] ; Mekary, Rania A. ^{[6, 7]} ; de Freitas, Ellen C. ^[3] ; da Silva, Adelino S. R. ^{[3, 1]}

Affiliation

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Postgrad Program Rehabil & Funct Performance, Av Bandeirantes 3900, BR-14040900 Ribeirao Preto, SP - Brazil

^[2] State Univ Sao Paulo, Dept Phys Educ, UNESP, Presidente Prudente, SP - Brazil

^[3] Univ Sao Paulo, Sch Phys Educ & Sport Ribeirao Preto, Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Ophthalmol, Ribeirao Preto, SP - Brazil

^[5] Univ Estadual Campinas, Sch Appl Sci, Lab Mol Biol Exercise LaBMEx, UNICAMP, Campinas, SP - Brazil

^[6] MCPHS Univ, Dept Pharmaceut Business & Adm Sci, Boston, MA - USA

^[7] Harvard Med Sch, Brigham & Womens Hosp, Dept Surg, Boston, MA - USA

• Document type: Journal article
• Source: Journal of Cellular Physiology; v. 233, n. 11, p. 8850-8861, NOV 2018.
• Web of Science Citations: 5

Abstract

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 -isoform of myosin heavy-chain gene expression, presenting signs of LV pathological hypertrophy development. (AU)

• FAPESP's process: 13/20591-3 - Responses of proteins from the inflammatory, insulinic and hypertrophic molecular pathways to nonfunctional overreaching induced by treadmill running performed in downhill, without inclination and uphill in skeletal muscle of mice
• Grantee: Adelino Sanchez Ramos da Silva
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/25459-9 - Nonfunctional overreaching in animal model: inflammatory and hypertrophic adaptions of the cardiac muscle
• Grantee: Alisson Luiz da Rocha
• Support Opportunities: Scholarships in Brazil - Master