Gene reprogramming in exercise-induced cardiac hypertrophy in swine: A transcriptional genomics approach

Kuster, Diederik W.D.; Merkus, Daphne; Blonden, Lau; Kremer, Andreas; IJcken, Wilfred F. J. van; Verhoeven, Adrie J.M.; Duncker, Dirk J.

doi:10.1016/j.yjmcc.2014.10.006

Cited by 11 publications

(7 citation statements)

References 45 publications

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“…In a swine model that had undergone treadmill running for 3-6 wk, the investigators reported that changes in gene expression observed in rodent models were not necessarily observed in swine. However, a common feature in the swine and previous rodent studies was the regulation of genes related to PI3K-Akt signaling (214). In this study, transcription factors differentially regulated between physiological and pathological hypertrophy were also identified including the glucocorticoid receptor and paired box 6 (Pax6; functional significance in the heart remains unclear) (214).…”

Section: Gene Expression Profilingmentioning

confidence: 79%

Understanding Key Mechanisms of Exercise-Induced Cardiac Protection to Mitigate Disease: Current Knowledge and Emerging Concepts

Bernardo

Ooi

Weeks

et al. 2018

Physiological Reviews

129

165

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The benefits of exercise on the heart are well recognized, and clinical studies have demonstrated that exercise is an intervention that can improve cardiac function in heart failure patients. This has led to significant research into understanding the key mechanisms responsible for exercise-induced cardiac protection. Here, we summarize molecular mechanisms that regulate exercise-induced cardiac myocyte growth and proliferation. We discuss in detail the effects of exercise on other cardiac cells, organelles, and systems that have received less or little attention and require further investigation. This includes cardiac excitation and contraction, mitochondrial adaptations, cellular stress responses to promote survival (heat shock response, ubiquitin-proteasome system, autophagy-lysosomal system, endoplasmic reticulum unfolded protein response, DNA damage response), extracellular matrix, inflammatory response, and organ-to-organ crosstalk. We summarize therapeutic strategies targeting known regulators of exercise-induced protection and the challenges translating findings from bench to bedside. We conclude that technological advancements that allow for in-depth profiling of the genome, transcriptome, proteome and metabolome, combined with animal and human studies, provide new opportunities for comprehensively defining the signaling and regulatory aspects of cell/organelle functions that underpin the protective properties of exercise. This is likely to lead to the identification of novel biomarkers and therapeutic targets for heart disease.

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Section: Gene Expression Profilingmentioning

confidence: 79%

Understanding Key Mechanisms of Exercise-Induced Cardiac Protection to Mitigate Disease: Current Knowledge and Emerging Concepts

Bernardo

Ooi

Weeks

et al. 2018

Physiological Reviews

129

165

View full text Add to dashboard Cite

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“…At the molecular level, reexpression of fetal genes is used as a biomarker of pathological cardiac hypertrophy. Among them, atrial and brain natriuretic peptide, ␣-skeletal myosin, and ␣-to ␤-myosin heavy chain (MHC) expression ratio have been the most frequently reported (45,51,102). Although the best known effects of atrial and brain natriuretic peptide are natriuresis and blood pressure regulation, these small peptides also contribute to preventing cardiac hypertrophy and fibrosis in the adult heart (66).…”

Section: Cardiac Remodeling Induced By Exercise Trainingmentioning

confidence: 99%

Aerobic exercise training promotes physiological cardiac remodeling involving a set of microRNAs

Fernandes

Baraúna

Negräo

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

130

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Fernandes T, Baraúna VG, Negrão CE, Phillips MI, Oliveira EM. Aerobic exercise training promotes physiological cardiac remodeling involving a set of microRNAs. Am J Physiol Heart Circ Physiol 309: H543-H552, 2015. First published June 12, 2015 doi:10.1152/ajpheart.00899.2014 hypertrophy is an important physiological compensatory mechanism in response to chronic increase in hemodynamic overload. There are two different forms of LV hypertrophy, one physiological and another pathological. Aerobic exercise induces beneficial physiological LV remodeling. The molecular/cellular mechanisms for this effect are not totally known, and here we review various mechanisms including the role of microRNA (miRNA). Studies in the heart, have identified antihypertrophic . Four miRNAs are recognized as cardiacspecific: miRNA-1, -133a/b, -208a/b, and -499 and called myomiRs. In our studies we have shown that miRNAs respond to swimming aerobic exercise by 1) decreasing cardiac fibrosis through miRNA-29 increasing and inhibiting collagen, 2) increasing angiogenesis through miRNA-126 by inhibiting negative regulators of the VEGF pathway, and 3) modulating the renin-angiotensin system through the miRNAs-27a/b and -143. Exercise training also increases cardiomyocyte growth and survival by swimming-regulated miRNA-1, -21, -27a/b, -29a/c, -30e, -99b, -100, -124, -126, -133a/b, -143, -144, -145, -208a, and -222 and running-regulated miRNA-1, -26, -27a, -133, -143, -150, and -222, which influence genes associated with the heart remodeling and angiogenesis. We conclude that there is a potential role of these miRNAs in promoting cardioprotective effects on physiological growth. cardiac hypertrophy; angiogenesis; swimming training; running training; microRNA THIS ARTICLE is part of a collection on Exercise Training in Cardiovascular Disease: Cell, Molecular, and Integrative Perspectives. Other articles appearing in this collection, as well as a full archive of all collections, can be found online at http://ajpheart.physiology.org/.EXERCISE TRAINING IS the most effective nonpharmacological intervention to reduce cardiovascular disease (CVD). Its prescription is recommended by the guidelines of the most important entities, such as the American College of Sport Medicine and the American Heart Association (39).Exercise training is well known to promote beneficial adaptations in the cardiovascular system which can vary according to type, intensity, and duration of exercise (32). Exercise training induces marked beneficial systemic effects on metabolism control, skeletal muscle, cognitive function, and cardiovascular function (30, 39). Among them, the set of adaptations induced in the myocardium are collectively referred to as "athlete's heart" and includes increased cardiac mass, formations of new blood vessels, and decreased collagen content (15a, 17, 20, 23, 77, 91). Individuals with high levels of physical activity have a lower prevalence and lower death rates from CVD (32, 86). Thus exercise training has been established not only as a way to ma...

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“…Given the need to access specific tissues and organs (e.g., brain, heart) and the need to control confounding variables (e.g., diet, environment, background genetics/epigenetics), animal models remain necessary. The National Institutes of Health recognized this form of “bidirectional translation” (Rubio et al 2010 ) as the ideal design for “a highly effective translational research program.” Indeed, multiple mammalian animal models have a long history of being used to understand basic principles of exercise physiology (e.g., Davis et al 2014 , Epp et al 2006 ; Ferguson et al 2014 ; Kao 1956 ; Poole et al 2007 ; Poole and Erickson 2011 ; Roberts et al 2014 ; Schaeffer et al 1996 ) and responses to repeated exercise (e.g., Favier et al 2016 ; Firshman et al 2015 ; Kuster et al 2014 ; Massett et al 2015 ). These models are adequate to model exercise responses using molecular techniques; however, it is critical that the model simulates and controls the human genetic heterogeneity underlying variable responses to exercise so that conclusions derived are both translatable and generalizable.…”

Section: Introductionmentioning

confidence: 99%

Inter-individual variation in adaptations to endurance and resistance exercise training: genetic approaches towards understanding a complex phenotype

2018

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Exercise training which meets the recommendations set by the National Physical Activity Guidelines ensues a multitude of health benefits towards the prevention and treatment of various chronic diseases. However, not all individuals respond well to exercise training. That is, some individuals have no response, while others respond poorly. Genetic background is known to contribute to the inter-individual (human) and -strain (e.g., mice, rats) variation with acute exercise and exercise training, though to date, no specific genetic factors have been identified that explain the differential responses to exercise. In this review, we provide an overview of studies in human and animal models that have shown a significant contribution of genetics in acute exercise and exercise training-induced adaptations with standardized endurance and resistance training regimens, and further describe the genetic approaches which have been used to demonstrate such responses. Finally, our current understanding of the role of genetics and exercise is limited primarily to the nuclear genome, while only a limited focus has been given to a potential role of the mitochondrial genome and its interactions with the nuclear genome to predict the exercise training-induced phenotype(s) responses. We therefore discuss the mitochondrial genome and literature that suggests it may play a significant role, particularly through interactions with the nuclear genome, in the inherent ability to respond to exercise.

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Gene reprogramming in exercise-induced cardiac hypertrophy in swine: A transcriptional genomics approach

Cited by 11 publications

References 45 publications

Understanding Key Mechanisms of Exercise-Induced Cardiac Protection to Mitigate Disease: Current Knowledge and Emerging Concepts

Understanding Key Mechanisms of Exercise-Induced Cardiac Protection to Mitigate Disease: Current Knowledge and Emerging Concepts

Aerobic exercise training promotes physiological cardiac remodeling involving a set of microRNAs

Inter-individual variation in adaptations to endurance and resistance exercise training: genetic approaches towards understanding a complex phenotype

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