Excessive training induces molecular signs of pathologic cardiac hypertrophy

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

Effect of Hibiscus Sabdariffa Linn on Il-6 and TNF- Α Levels in Overtrained Rat Heart

“…This study showed that overtraining increased the TNF-α level and tended to increase the IL-6 level in the heart, consistent with other studies [4,15,16]. Overtraining has been proved to induce acute local inflammation, which may develop into chronic inflammation, thus producing systemic inflammation.…”

“…The symptoms of OTS are varied, and they include fatigue, depression, bradycardia, loss of motivation, insomnia, irritability, agitation, tachycardia, hypertension, restlessness, anorexia, weight loss, lack of mental concentration, stiff muscles, anxiety, and awakening unrefreshed [3]. In mice, OTS led to left ventricular hypertrophy and increased gene expression related to pathological hypertrophy, such as mRNA for the ANP, mRNA for β-myosin heavy chain, and mRNA for skeletal muscle actin [4].…”

Postinfarction exercise training alleviates cardiac dysfunction and adverse remodeling via mitochondrial biogenesis and SIRT1/PGC‐1α/PI3K/Akt signaling

“…For example, it was reported that 16 weeks of habitual voluntary wheel running had no effects on myocardial collagen concentration and cross-linking in the rat left ventricle, although cardiac stiffness was reduced (Woodiwiss, Oosthuyse, & Norton, 1998). We speculate that the mild enhancement of collagen I expression represents an adaptive response of heart to exercise stress as recently reported by da Rocha et al (2018) and is substantially different from the robust increase of collagen I expression following MI, which led to pathologic fibrosis in the heart (Figure 3). In fact, another study showed that exercise training prevented the decline in mRNA of collagen I and III in middle-aged rats and attenuated the decline in senescent animals (Thomas, Zimmerman, Hansen, Martin, & McCormick, 2000).…”

Role of the TRPM4 Channel in Cardiovascular Physiology and Pathophysiology

“…Under the physiological condition, the cardiac function can be performed in an orderly manner [ 93 ]. However, if it exceeds the range of compensation owing to cardiac pressure or volume overload, such as high levels of angiotensin II (AII), chronic hypertension, valvular dysfunction, myocardial infarction, and even excessive training, the hypertrophy shifts to an irreversible pathology, which induces severe arrhythmia or cardiac failure [ 22 , 103 , 104 , 105 , 106 ].…”