Aerobic Fitness Is Associated With Cardiomyocyte Contractile Capacity and Endothelial Function in Exercise Training and Detraining

Kemi, Ole Johan; Haram, Per Magnus; Wisløff, Ulrik; Ellingsen, Øyvind

doi:10.1161/01.cir.0000129308.04757.72

Cited by 114 publications

(136 citation statements)

References 34 publications

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“…The cellular basis for this involves improved contractile function of the cardiomyocyte, which we have demonstrated occurs with exercise training in rats [1][2][3]. The present study confirms that these changes occur in cardiomyocytes isolated from exercise trained mice, and identify sub-cellular mechanisms that contribute to improved inotropy and lusitropy.…”

Section: Aerobic Interval Training Up-regulates Serca-2a Plb and Camksupporting

confidence: 82%

“…Aerobic interval training-induced improvement of diastolic function was demonstrated by the faster rates of cardiomyocyte re-lengthening and decay of the Ca 2+ transient, in line with exercise trained rats [1][2][3]. These effects were partly dependent upon CaMKII being available in the cytosol, as CaMK-inhibition by AIP partly removed the exercise traininginduced effects when cells were paced at frequencies as close to physiological mouse heart rates as experimentally possible.…”

Section: Aerobic Interval Training Improves Cardiomyocyte Lusitropymentioning

confidence: 57%

“…Improved myofilament sensitivity to Ca 2+ is an important adaptation of the rat heart to regular exercise training [1][2][3]21], and is now also indicated in the mouse heart. The CaMKblockade maneuver in trained cardiomyocytes caused Ca 2+ sensitivity to revert toward levels closer to sedentary controls; hence, suggesting that CaMK partly modulates the traininginduced improvement in Ca 2+ sensitivity.…”

Section: Myofilament Ca 2+ Sensitivitymentioning

confidence: 99%

“…We have previously shown that aerobic capacity is closely related to cardiomyocyte contractility and calcium handling in training [1,2], detraining [3], post-infarction heart failure [4] and genetic selection of high versus low exercise capacity [5]. It has also been demonstrated that exercise-induced improvement of contractile function in cardiomyocytes may be linked to increased activity of the cardiac sarcoplasmic reticulum Ca 2+ ATPase 2a (SERCA-2a) both in healthy rats [2,6] and in rats with post-infarction heart failure [4].…”

Section: Introductionmentioning

confidence: 99%

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Aerobic interval training enhances cardiomyocyte contractility and Ca2+ cycling by phosphorylation of CaMKII and Thr-17 of phospholamban

Kemi

Ellingsen

Ceci

et al. 2007

Journal of Molecular and Cellular Cardiology

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114

116

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Cardiac adaptation to aerobic exercise training includes improved cardiomyocyte contractility and calcium handling. Our objective was to determine whether cytosolic calcium/calmodulindependent kinase II and its downstream targets are modulated by exercise training. A six-week aerobic interval training program by treadmill running increased maximal oxygen uptake by 35% in adult mice, whereupon left ventricular cardiomyocyte function was studied and myocardial tissue samples were used for biochemical analysis. Cardiomyocytes from trained mice had enhanced contractility and faster relaxation rates, which coincided with larger amplitude and faster decay of the calcium transient, but not increased peak systolic calcium levels. These changes were associated with reduced phospholamban expression relative to sarcoplasmic reticulum calcium ATPase, and constitutively increased phosphorylation of phospholamban at the threonine 17, but not at the serine 16 site. Calcium-calmodulin-dependent kinase IIδ phosphorylation was increased at Threonine 287, indicating activation. To investigate the physiological role of calcium/ calmodulin-dependent kinase IIδ phosphorylation, this kinase was blocked specifically by autocamtide-2 related inhibitory peptide II. This maneuver completely abolished training-induced improvements of cardiomyocyte contractility and calcium handling, and blunted, but did not completely abolish the training-induced increase in Ca 2+ sensitivity. Also, inhibition of calcium/ calmodulin-dependent kinase II reduced the greater frequency-dependent acceleration of relaxation that was observed after aerobic interval training. These observations indicate that calcium/calmodulin-dependent kinase IIδ contributes significantly to the functional adaptation of the cardiomyocyte to regular exercise training.

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Section: Aerobic Interval Training Up-regulates Serca-2a Plb and Camksupporting

confidence: 82%

Section: Aerobic Interval Training Improves Cardiomyocyte Lusitropymentioning

confidence: 57%

Section: Myofilament Ca 2+ Sensitivitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Aerobic interval training enhances cardiomyocyte contractility and Ca2+ cycling by phosphorylation of CaMKII and Thr-17 of phospholamban

Kemi

Ellingsen

Ceci

et al. 2007

Journal of Molecular and Cellular Cardiology

Self Cite

114

116

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“…For example, 4-8 weeks detraining in humans caused the endothelin-1 and nitric oxide to return to basal levels, these being two molecules involved in exercise-regulated signaling towards the vascular endothelium (Maeda et al 2001). Furthermore, 2-4 weeks of detraining in rats regressed a number of cardiomyocyte parameters associated with aerobic Wtness to pre-training values (Kemi et al 2004) However, to the best of our knowledge, the eVects of detraining on myocardial angiogenesis remain to be investigated.…”

Section: Introductionmentioning

confidence: 99%

Partial persistence of exercise-induced myocardial angiogenesis following 4-week detraining in the rat

Marini

Falcieri

Margonato

et al. 2008

Histochem Cell Biol

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Enhanced angiogenesis, or capillary growth, has a prominent role among the various beneWcial eVects of exercise training on the myocardium. The aim of the present study is to assess if training-induced increases in capillarity and vascularization persist after 4 weeks of detraining. Adult male rats were trained to run on a treadmill for 10 weeks at »60% VO 2max , which did not induce cardiac hypertrophy, but increased (P < 0.05) the soleus/ body weight ratio, left ventricle capillarity and von Willebrand-positive cell density (n = 6). In another group of animals (n = 6) subjected to training followed by 4-week detraining, the soleus/body weight ratio returned to normal, with only partial reversal of left ventricle capillarity and von Willebrand-positive cell density. Markers of angiogenesis (VEGF, KDR/VEGF-R2 and HIF-1 mRNA, studied by real-time RT-PCR) were upregulated at the end of training, and returned to baseline value after detraining. Electron microscopy highlighted some morphological features in trained hearts (endothelial cell sprouting and bridges and pericyte detachment), suggestive of endothelial cell proliferation and capillary growth that were absent in untrained and detrained hearts. We conclude that the training-induced increase in cardiac capillarity and vascularization are retained for some time upon cessation of the training program even in the absence of angiogenic stimuli.

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Electrically stimulated in vitro heart cell mimic of acute exercise reveals novel immediate cellular responses to exercise: Reduced contractility and metabolism, but maintained calcium cycling and increased myofilament calcium sensitivity

Costa,

Ghouri,

Johnston

et al. 2023

Cell Biochemistry & Function

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Cardiac cellular responses to acute exercise remain undescribed. We present a model for mimicking acute aerobic endurance exercise to freshly isolated cardiomyocytes by evoking exercise‐like contractions over prolonged periods of time with trains of electrical twitch stimulations. We then investigated immediate contractile, Ca2+, and metabolic responses to acute exercise in perfused freshly isolated left ventricular rat cardiomyocytes, after a matrix‐design optimized protocol and induced a mimic for acute aerobic endurance exercise by trains of prolonged field twitch stimulations. Acute exercise decreased cardiomyocyte fractional shortening 50%–80% (p < .01). This was not explained by changes to intracellular Ca2+ handling (p > .05); rather, we observed a weak insignificant Ca2+ transient increase (p = .11), while myofilament Ca2+ sensitivity increased 20%–70% (p < .05). Acidic pH 6.8 decreased fractional shortening 20%–70% (p < .05) because of 20%–30% decreased Ca2+ transients (p < .05), but no difference occurred between control and acute exercise (p > .05). Addition of 1 or 10 mM La− increased fractional shortening in control (1 mM La−: no difference, p > .05; 10 mM La−: 20%–30%, p < .05) and acute exercise (1 mM La−: 40%–90%, p < .01; 10 mM La−: 50%–100%, p < .01) and rendered acute exercise indifferent from control (p > .05). Intrinsic autofluorescence showed a resting NADstate of 0.59 ± 0.04 and FADstate of 0.17 ± 0.03, while acute exercise decreased NADH/FAD ratio 8% (p < .01), indicating intracellular oxidation. In conclusion, we show a novel approach for studying immediate acute cardiomyocyte responses to aerobic endurance exercise. We find that acute exercise in cardiomyocytes decreases contraction, but Ca2+ handling and myofilament Ca2+ sensitivity compensate for this, while acidosis and reduced energy substrate and mitochondrial ATP generation explain this.

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Aerobic Fitness Is Associated With Cardiomyocyte Contractile Capacity and Endothelial Function in Exercise Training and Detraining

Cited by 114 publications

References 34 publications

Aerobic interval training enhances cardiomyocyte contractility and Ca2+ cycling by phosphorylation of CaMKII and Thr-17 of phospholamban

Aerobic interval training enhances cardiomyocyte contractility and Ca2+ cycling by phosphorylation of CaMKII and Thr-17 of phospholamban

Partial persistence of exercise-induced myocardial angiogenesis following 4-week detraining in the rat

Electrically stimulated in vitro heart cell mimic of acute exercise reveals novel immediate cellular responses to exercise: Reduced contractility and metabolism, but maintained calcium cycling and increased myofilament calcium sensitivity

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