Cardiac Energetic Metabolism Research Articles

The pivotal role of miRNA-21 in myocardial metabolic flexibility in response to short- and long-term high glucose treatment: Evidence in human cardiomyocyte cell line

AimmiRNA-21 is a crucial regulator of developing cardiac diseases, but its role is still controversial, and therefore it is necessary to clarify, at cardiac level, its involvement in high glucose induced-acute and chronic cardiac damage. MethodsHuman ventricular cardiac myoblasts AC16, treated and not with miRNA-21 inhibitor, were exposed to high glucose for 2 and 7 days, and the expression of damage markers were investigated. Further, cardiac energetic metabolism was evaluated by measuring both the expression of glucose transporters and lipids regulators. ResultsShort-term high glucose treatment induced a significant increase in miRNA-21 expression (p < 0.05) that was associated with an increase in hydrogen ion flux and energy potential dissipation without any change in energy production or increase in genes expression involved in cellular damage. miRNA-21 reduction observed (p < 0.05) at 7 days of high glucose treatment, induced the activation of damage pathways and compromised mitochondrial function (p < 0.05). ConclusionIn human cardiomyocytes, the abundance of miRNA-21 takes part in first defense mechanism against cardiac insult and its cardioprotective effect depends on time of exposure to injury. Moreover, miRNA-21 regulates mitochondrial respiration and the ability of cells to select the most appropriate substrate for ATP production in given environment.

Impact of Modality and Intensity of Early Exercise Training on Ventricular Remodeling after Myocardial Infarction.

The objective of this study was to analyze the impact of different modalities and intensities of exercise training on cardiac remodeling started early after experimental myocardial infarction (MI). Male Wistar rats, weighing 200–250 g, were subjected to experimental MI. After 5 days, the animals were allocated into three experimental groups and observed for three months: S (sedentary control animals), C (animals subjected to continuous low-intensity training), and HIT (animals subjected to high-intensity interval training). Low-intensity exercise training was performed at a treadmill speed corresponding to 40% VO2 max, which was kept unchanged throughout the entire session (i.e., continuous low-intensity training). High-intensity interval training was performed in such a way that rats run during 3 min at 60% VO2 max, followed by 4-minute intervals at 85% VO2 max (i.e., high-intensity interval training). After the follow-up period, we studied hypertrophy and ventricular geometry, functional alterations in vivo and in vitro, oxidative stress, apoptosis, and cardiac energetic metabolism. Our data showed that both high-intensity interval and continuous low-intensity modalities improved cardiac energetic metabolism variables in comparison with sedentary infarcted animals. In addition, high-intensity interval training decreased cardiac oxidative stress, associated with improved diastolic function. On the other hand, the continuous low-intensity group showed impairment of cardiac function. Therefore, altogether, our data suggest that high-intensity interval training could be the best modality for early physical exercise after MI and should be better studied in this clinical scenario.

Involvement of the phosphoryl transfer network on cardiac energetic metabolism during Staphylococcus aureus infection and its association to disease pathophysiology

Evidences have suggested that the phosphoryl transfer network by the enzymatic activities of creatine kinase (CK), adenylate kinase (AK), pyruvate kinase (PK), and lactate dehydrogenase (LDH), shows new perspectives to understand some disturbances in the energy metabolism during bacterial infections. Thus, the aim of this study was to evaluate whether Staphylococcus aureus infection in mice could alter serum and cardiac activities of these enzymes and their association to disease pathophysiology. For that, we measured total leukocytes, lymphocytes and neutrophils (just 48 h of infection) that were lower in infected animals after 48 and 72 h in infected mice compared with negative control, while total protein and globulin plasma levels were higher after 72 h of infection. The serum CK activity was higher in infected animals 48 and 72 h post-infection compared to the control group, as well as observed for mitochondrial cardiac CK activity. The serum PK activity was higher in infected animals after 72 h of infection compared to the control group, and lower in the cardiac tissue. The cardiac AK activity was lower in infected animals 48 h and 72 h post-infection compared to the control group, while serum and cardiac LDH activities were higher. Based on these evidences, it is possible to conclude that the stimulation of CK activity exerts a key role as an attempt to maintain the bioenergetic homeostasis by the production of phosphocreatine to avoid a rapid fall on the concentrations of total adenosine triphosphate. In summary, the phosphoryl transfer network can be considered a pathway involved in the improvement on tissue and cellular energy homeostasis of S. aureus-infected mice.

Exercise-Induced Decrease in Myocardial High-Energy Phosphate Metabolites in Patients With Chagas Heart Disease

BackgroundThe influence of exercise on cardiac metabolic response in patients with Chagas disease is incompletely understood. Methods and ResultsChanges in cardiac energetic metabolism were investigated in Chagas disease patients before and during isometric handgrip exercise with 31P magnetic resonance spectroscopy (MRS). Twenty-eight patients (10 with systolic dysfunction: group I; 10 with normal systolic function and electrocardiogram (ECG) abnormalities: group II; and 8 asymptomatic without ECG abnormalities: group III) and 8 healthy control subjects (group C) were evaluated by electrocardiogram, echocardiogram, functional tests for coronary artery disease, and image-selected localized cardiac 31P-MRS. The myocardial phosphocreatine to [β-phosphate]adenosine triphosphate ratio (PCr/β-ATP) was measured at rest and during isometric handgrip exercise. Exercise testing or 99mTc–sestamibi scintigraphy were negative for myocardial ischemia in all individuals. At rest, cardiac PCr/β-ATP was decreased in all Chagas groups (1.23 ± 0.37) versus group C (1.88 ± 0.08; P < .001) and was lower in group I (0.89 ± 0.24) versus groups II (1.44 ± 0.23) and III (1.40 ± 0.37; P < .001). There was no stress-induced change in cardiac PCr/β-ATP (1.88 ± 0.08 at rest vs 1.89 ± 0.08 during exercise; P = NS) in group C. Mean cardiac PCr/β-ATP was 0.89 ± 0.24 and 0.56 ± 0.21 at rest and during exercise, respectively, in group I (37% decrease; P < .001). In group II, PCr/β-ATP was 1.44 ± 0.23 at rest and 0.97 ± 0.37 during exercise (33% decrease; P < .001). In group III, PCr/β-ATP was 1.40 ± 0.37 at rest and 0.60 ± 0.19 during exercise (57% decrease; P < .001). ConclusionsMyocardial high-energy phosphates are reduced at rest in Chagas heart disease patients, and the reduction is greater in patients with left ventricular dysfunction. Regardless of left ventricular function, Chagas patients exhibit an exercise-induced decline in cardiac high-energy phosphates consistent with myocardial ischemia, suggesting the possibility that this metabolic approach may offer a tool to probe new interventions in Chagas disease patients.

Influence of different doses of retinoic acid on cardiac remodeling

Objective The role of retinoic acid in promoting postnatal heart alterations is still unclear. The aim of this study was to evaluate whether the cardiac alterations caused by all-trans- retinoic acid (ATRA) in normal adult rat hearts are physiologic or pathologic and if these alterations are dose-dependent. Methods Rats were allocated into a control group that received a diet without ATRA ( n = 16), a group that received 0.3 mg of ATRA/kg of diet ( n = 17), a group that received a diet containing 10 mg of ATRA/kg ( n = 18), or a group that received 50 mg of ATRA/kg in the diet ( n = 18). After 4 wk, the animals were evaluated echocardiographically, morphologically, and biochemically. Results The 50-mg ATRA group presented cardiac hypertrophy with maintenance of cardiac geometry and increased systolic function, whereas diastolic function was similar to that of the control group. In addition, progressive increases in the ATRA dose resulted in gradual augmentations of left atrial diameter, left ventricular diastolic and systolic diameters, left ventricular mass index, cardiac output, cardiac index, and aortic velocity. The ATRA did not produce alterations in interferon-γ and tumor necrosis factor-α cardiac levels, interstitial collagen volume fraction, or the intensity and localization of connexin-43. In addition, no alteration was observed in β-hydroxyacyl coenzyme A dehydrogenase, lactate dehydrogenase, or citrate synthase, suggesting that cardiac energetic metabolism was preserved with ATRA. Conclusion These results suggest that ATRA produced dose-dependent effects and cardiac remodeling that is more compatible with a physiologic response.

Dietary fish oil promotes positive inotropy and efficiency of digitalis.

Digitalis is clinically effective in heart failure, but it has an extremely narrow therapeutic index. Inclusion of fish oil (FO) in the diet may have cardioprotective effects by different mechanisms (1,2): decreased heart rate and occurrence of arrhythmias, increased mechanical activity, and ejection fraction. The aim of this study was to investigate if dietary FO with incorporation of n-3 polyunsaturated fatty acids in membranes could promote positive inotropy of ouabain. Methods. Twenty-five male Wistar rats were fed for 60 d: (i) supplemented with FO concentrate [180 mg eicosapentaenoic acid (EPA) + 120 mg docosahexaenoic acid (DHA)/g oil] at a dose of 0.5 g/kg/d (group FO), (ii) without supplementation (group C). Inotropic and toxic responses to cumulative doses of ouabain (from 100 nM to 0.3 raM) were evaluated in the isolated perfused rat heart and the relative variations in cardiac energetic metabolism, and pH were obtained using 3tp magnetic resonance spectroscopy. Activity, contribution, affinity, and expression of Na,K-ATPase isoforms were determined on purified membrane-bound Na,K-ATPase. Fatty acid composition of cardiac membrane fractions was analyzed by gas chromatography. Results. The rat is the only mammalian species with a well-characterized biphasic inotropic response to ouabain which is coupled to consecutive inhibition of the cx2- and o~[isoforms of high and low affinity for ouabain, respectively. Results show that (i) there is a twofold increase in the lowaffinity response to ouabain (0.1 mM) (% inotropy = 40 _+ 3 in group C vs. 79 -+ 7 in group FO, P < 0.001), (ii) there is a lower inhibition of ctl Na,K-ATPase activity (ICs0 = 7.2 _+ 2.0 × 10 -5 M in group C and 3.4 _+ 0.8 × 10 -4 M in group FO, P < 0.05), (iii) the higher inotropic response to ouabain is not associated with significant changes in energetics, (iv) alteration of function and energetics in response to the toxic dose of 0.3 mM is delayed in the FO group, (v) there are no differences in overall Na,K-ATPase activity or in the proportion of its isoforms, and (vi) fatty acid composition of rat hearts submitted to FO diet shows that the proportion of EPA and DHA had significantly risen. In conclusion, improving ouabain efficacy may represent an additional mechanism whereby FO exert their cardioprotective action in rats and possibly in humans. Acknowledgment. This work was supported in part by grants of the French Ministry of Health (PHRC, UF t638 and UF 1673), by MRT (grant 650994), CNRS (UMR 6612 and URA 1829), and the Assistance Publique-H6pitaux de Marseille.

Action potential modifications in rat myocardial cells during vitamin A deficiency.

Ventricular cell action potentials were measured in situ using intracellular microelectrodes in the hearts of vitamin A‐deficient rats, both at the spontaneous heart rate and at rates increased to various higher levels. The changes found indicate that a lack of vitamin A in the tissue may modify the ion permeability underlying cardiac electrogenesis, without affecting cardiac energetic metabolism. Results are discussed in the light of recent theories that vitamin A may stabilize the structure of cell membranes and control their permeability.