scholarly journals Contraction–relaxation coupling is unaltered by exercise training and infarction in isolated canine myocardium

2021 ◽  
Vol 153 (7) ◽  
Author(s):  
Farbod Fazlollahi ◽  
Jorge J. Santini Gonzalez ◽  
Steven J. Repas ◽  
Benjamin D. Canan ◽  
George E. Billman ◽  
...  
Keyword(s):  
Exercise Training ◽  
Myosin Binding Protein ◽  
Myosin Binding Protein C ◽  
Training History ◽  
Maximal Speed ◽  
Myosin Binding ◽  
Contraction And Relaxation ◽  
Surgically Induced ◽  
Ventricular Trabeculae ◽  
Canine Myocardium

The two main phases of the mammalian cardiac cycle are contraction and relaxation; however, whether there is a connection between them in humans is not well understood. Routine exercise has been shown to improve cardiac function, morphology, and molecular signatures. Likewise, the acute and chronic changes that occur in the heart in response to injury, disease, and stress are well characterized, albeit not fully understood. In this study, we investigated how exercise and myocardial injury affect contraction–relaxation coupling. We retrospectively analyzed the correlation between the maximal speed of contraction and the maximal speed of relaxation of canine myocardium after receiving surgically induced myocardial infarction, followed by either sedentary recovery or exercise training for 10–12 wk. We used isolated right ventricular trabeculae, which were electrically paced at different lengths, frequencies, and with increasing β-adrenoceptor stimulation. In all conditions, contraction and relaxation were linearly correlated, irrespective of injury or training history. Based on these results and the available literature, we posit that contraction–relaxation coupling is a fundamental myocardial property that resides in the structural arrangement of proteins at the level of the sarcomere and that this may be regulated by the actions of cardiac myosin binding protein C (cMyBP-C) on actin and myosin.

scholarly journals Increased VO2 peak after a structured exercise-training program is associated with reduced levels of cardiac myosin binding protein C in patients with symptomatic chronic heart failure

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
E.A Riveland ◽  
T Valborgland ◽  
A Ushakova ◽  
T Karlsen ◽  
C Delagardelle ◽  
...  
Keyword(s):  
Heart Failure ◽  
Exercise Training ◽  
Training Program ◽  
Plasma Levels ◽  
Intervention Group ◽  
Cardiac Myosin ◽  
Myosin Binding Protein ◽  
Myosin Binding Protein C ◽  
Exercise Training Program ◽  
Myosin Binding

Abstract Background Cardiac myosin-binding protein C (cMyC), a cardiac contractile protein, is a novel biomarker of myocardial injury, rising earlier and disappearing faster than cardiac troponins. It is a promising biomarker for use in triage of patients with chest pain presenting in the emergency department. It also has prognostic significance in patients with heart failure. However, the effects of systematic exercise training on plasma levels of cMyC has previously not been evaluated. Purpose The aim of this study was to assess the effect of a 12-week exercise training program on changes in plasma levels of cMyC in patients with chronic symptomatic heart failure with reduced ejection fraction (HFrEF). The changes in plasma levels of cMyC in an intervention group, performing structured exercise programs, were compared to those in a control group, instructed to perform regular recommended exercise (RRE) according to current guidelines. Methods This was a post hoc analysis of the SMARTEX-HF trial in 215 patients with symptomatic HF with Left Ventricular Ejection Fraction (LVEF) <35% and NYHA II-III. The patients were randomly assigned to High Intensity Interval Training (HIIT, n=77), Moderate Continuous Training (MCT, n=65) or RRE, (n=73) for 12 weeks. HIIT and MCT groups constituted the intervention group (IG). Measurements and clinical data were acquired before and after the 12-week intervention. Statistical analysis We divided the patients in two groups with Δ VO2Peak above and below the median of the sample. The absolute changes of cMyC were then compared between the two groups. Mann-Whitney U test was used to compare continuous variables between the groups. Chi-squared test and Fisher exact test were used to compare categorical variables, as appropriate. A two-tailed p<0.05 was considered significant. Results There were no differences in changes of cMyC plasma levels, measured at baseline and after the intervention, between patients in the IG and RRE-group (p=0.580). When dividing the entire study population according to Δ VO2Peak higher or lower than median value 0.48 ml/kg/min, we found a statistically significant greater reduction of cMyC values after 12 weeks of exercise training for those with higher than median Delta VO2Peak values compared to those with lower values (p=0.012). This finding was even stronger for the percentage change in cMyC levels (p=0.004 between groups). Conclusion In patients with symptomatic chronic HFrEF performing a structured 12-week exercise training program, a greater increase in Δ VO2Peak is significantly associated with a reduction in cMyC, suggesting cMyC may provide a dynamic measure of cardiorespiratory state. FUNDunding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Central Norwegian Health authority,Norwegian University of Science and Technology Baseline characteristics Boxplot cMyC vs peak VO2

scholarly journals Kinetics of cardiac muscle contraction and relaxation are linked and determined by properties of the cardiac sarcomere

2010 ◽  
Vol 299 (4) ◽  
pp. H1092-H1099 ◽  
Author(s):  
Paul M. L. Janssen
Keyword(s):  
Myocardial Contraction ◽  
Adrenergic Stimulation ◽  
Physiological Mechanisms ◽  
Cardiac Sarcomere ◽  
Myosin Binding Protein ◽  
Myosin Binding Protein C ◽  
Speed Up ◽  
Myosin Binding ◽  
Contraction And Relaxation ◽  
Kinetics Of

The regulation of myocardial contraction and relaxation kinetics is currently incompletely understood. When the amplitude of contraction is increased via the Frank-Starling mechanism, the kinetics of the contraction slow down, but when the amplitude of contraction is increased with either an increase in heart rate or via β-adrenergic stimulation, the kinetics speed up. It is also unknown how physiological mechanisms affect the kinetics of contraction versus those of relaxation. We investigated contraction-relaxation coupling in isolated trabeculae from the mouse and rat and stimulated them to contract at various temperatures, frequencies, preloads, and in the absence and presence of β-adrenergic stimulation. In each muscle at least 16 different conditions were assessed, and the correlation coefficient of the speed of contraction and relaxation was very close (generally >0.98). Moreover, in all but one of the analyzed murine strains, the ratio of the minimum rate of the derivative of force development (dF/d t) over maximum dF/d t was not significantly different. Only in trabeculae isolated from myosin-binding protein-C mutant mice was this ratio significantly lower (0.61 ± 0.07 vs. 0.84 ± 0.02 in 11 other strains of mice). Within each strain, this ratio was unaffected by modulation of length, frequency, or β-adrenergic stimulation. Rat trabeculae showed identical results; the balance between kinetics of contraction and relaxation was generally constant (0.85 ± 0.04). Because of the great variety in underlying excitation-contraction coupling in the assessed strains, we concluded that contraction-relation coupling is a property residing in the cardiac sarcomere.

scholarly journals Making waves: A proposed new role for myosin-binding protein C in regulating oscillatory contractions in vertebrate striated muscle

2020 ◽  
Vol 153 (3) ◽  
Author(s):  
Samantha P. Harris
Keyword(s):  
Protein C ◽  
Molecular Mechanisms ◽  
Striated Muscle ◽  
Binding Protein ◽  
Muscle Performance ◽  
Central Position ◽  
Myosin Binding Protein ◽  
Myosin Binding Protein C ◽  
Myosin Binding ◽  
Contraction And Relaxation

Myosin-binding protein C (MyBP-C) is a critical regulator of muscle performance that was first identified through its strong binding interactions with myosin, the force-generating protein of muscle. Almost simultaneously with its discovery, MyBP-C was soon found to bind to actin, the physiological catalyst for myosin’s activity. However, the two observations posed an apparent paradox, in part because interactions of MyBP-C with myosin were on the thick filament, whereas MyBP-C interactions with actin were on the thin filament. Despite the intervening decades since these initial discoveries, it is only recently that the dual binding modes of MyBP-C are becoming reconciled in models that place MyBP-C at a central position between actin and myosin, where MyBP-C alternately stabilizes a newly discovered super-relaxed state (SRX) of myosin on thick filaments in resting muscle and then prolongs the “on” state of actin on thin filaments in active muscle. Recognition of these dual, alternating functions of MyBP-C reveals how it is central to the regulation of both muscle contraction and relaxation. The purpose of this Viewpoint is to briefly summarize the roles of MyBP-C in binding to myosin and actin and then to highlight a possible new role for MyBP-C in inducing and damping oscillatory waves of contraction and relaxation. Because the contractile waves bear similarity to cycles of contraction and relaxation in insect flight muscles, which evolved for fast, energetically efficient contraction, the ability of MyBP-C to damp so-called spontaneous oscillatory contractions (SPOCs) has broad implications for previously unrecognized regulatory mechanisms in vertebrate striated muscle. While the molecular mechanisms by which MyBP-C can function as a wave maker or a wave breaker are just beginning to be explored, it is likely that MyBP-C dual interactions with both myosin and actin will continue to be important for understanding the new functions of this enigmatic protein.

Biological variation of cardiac myosin-binding protein C in healthy individuals

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Bashir Alaour ◽  
Torbjørn Omland ◽  
Janniche Torsvik ◽  
Thomas E. Kaier ◽  
Marit S. Sylte ◽  
...  
Keyword(s):  
Risk Stratification ◽  
Protein C ◽  
Myocardial Injury ◽  
Binding Protein ◽  
Biological Variation ◽  
Cardiac Myosin ◽  
Analytical Quality ◽  
Myosin Binding Protein ◽  
Myosin Binding Protein C ◽  
Myosin Binding

Abstract Objectives Cardiac myosin-binding protein C (cMyC) is a novel biomarker of myocardial injury, with a promising role in the triage and risk stratification of patients presenting with acute cardiac disease. In this study, we assess the weekly biological variation of cMyC, to examine its potential in monitoring chronic myocardial injury, and to suggest analytical quality specification for routine use of the test in clinical practice. Methods Thirty healthy volunteers were included. Non-fasting samples were obtained once a week for ten consecutive weeks. Samples were tested in duplicate on the Erenna® platform by EMD Millipore Corporation. Outlying measurements and subjects were identified and excluded systematically, and homogeneity of analytical and within-subject variances was achieved before calculating the biological variability (CVI and CVG), reference change values (RCV) and index of individuality (II). Results Mean age was 38 (range, 21–64) years, and 16 participants were women (53%). The biological variation, RCV and II with 95% confidence interval (CI) were: CVA (%) 19.5 (17.8–21.6), CVI (%) 17.8 (14.8–21.0), CVG (%) 66.9 (50.4–109.9), RCV (%) 106.7 (96.6–120.1)/−51.6 (−54.6 to −49.1) and II 0.42 (0.29–0.56). There was a trend for women to have lower CVG. The calculated RCVs were comparable between genders. Conclusions cMyC exhibits acceptable RCV and low II suggesting that it could be suitable for disease monitoring, risk stratification and prognostication if measured serially. Analytical quality specifications based on biological variation are similar to those for cardiac troponin and should be achievable at clinically relevant concentrations.

scholarly journals The Interplay between S-glutathionylation and Phosphorylation of Cardiac Troponin I and Myosin Binding Protein C in End-Stage Human Failing Hearts

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1134
Author(s):  
Heidi Budde ◽  
Roua Hassoun ◽  
Melina Tangos ◽  
Saltanat Zhazykbayeva ◽  
Melissa Herwig ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein C ◽  
Troponin I ◽  
Reduced Glutathione ◽  
Binding Protein ◽  
Enzyme Treatment ◽  
Myosin Binding Protein ◽  
Myosin Binding Protein C ◽  
Myosin Binding ◽  
End Stage

Oxidative stress is defined as an imbalance between the antioxidant defense system and the production of reactive oxygen species (ROS). At low levels, ROS are involved in the regulation of redox signaling for cell protection. However, upon chronical increase in oxidative stress, cell damage occurs, due to protein, DNA and lipid oxidation. Here, we investigated the oxidative modifications of myofilament proteins, and their role in modulating cardiomyocyte function in end-stage human failing hearts. We found altered maximum Ca2+-activated tension and Ca2+ sensitivity of force production of skinned single cardiomyocytes in end-stage human failing hearts compared to non-failing hearts, which was corrected upon treatment with reduced glutathione enzyme. This was accompanied by the increased oxidation of troponin I and myosin binding protein C, and decreased levels of protein kinases A (PKA)- and C (PKC)-mediated phosphorylation of both proteins. The Ca2+ sensitivity and maximal tension correlated strongly with the myofilament oxidation levels, hypo-phosphorylation, and oxidative stress parameters that were measured in all the samples. Furthermore, we detected elevated titin-based myocardial stiffness in HF myocytes, which was reversed by PKA and reduced glutathione enzyme treatment. Finally, many oxidative stress and inflammation parameters were significantly elevated in failing hearts compared to non-failing hearts, and corrected upon treatment with the anti-oxidant GSH enzyme. Here, we provide evidence that the altered mechanical properties of failing human cardiomyocytes are partially due to phosphorylation, S-glutathionylation, and the interplay between the two post-translational modifications, which contribute to the development of heart failure.

scholarly journals Cardiac Myosin-Binding Protein C Modulates the Tuning of the Molecular Motor in the Heart

2008 ◽  
Vol 95 (2) ◽  
pp. 720-728 ◽  
Author(s):  
Yves Lecarpentier ◽  
Nicolas Vignier ◽  
Patricia Oliviero ◽  
Aziz Guellich ◽  
Lucie Carrier ◽  
...  
Keyword(s):  
Protein C ◽  
Molecular Motor ◽  
Binding Protein ◽  
Cardiac Myosin ◽  
Myosin Binding Protein ◽  
Myosin Binding Protein C ◽  
Myosin Binding
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