scholarly journals Light Emitting Diodes Photobiomodulation Improves Cardiac Function by Promoting ATP Synthesis in Mice With Heart Failure

2021 ◽  
Vol 8 ◽  
Author(s):  
Wenwen Zhang ◽  
Xinlu Gao ◽  
Xiuxiu Wang ◽  
Desheng Li ◽  
Yiming Zhao ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Light Emitting Diodes ◽  
Contractile Function ◽  
Atp Synthesis ◽  
High Morbidity ◽  
Effective Wavelength ◽  
Light Emitting ◽  
Beneficial Effects ◽  
The Common

Heart failure (HF) is the common consequences of various cardiovascular diseases, often leading to severe cardiac output deficits with a high morbidity and mortality. In recent years, light emitting diodes-based therapy (LEDT) has been widely used in multiple cardiac diseases, while its modulatory effects on cardiac function with HF still remain unclear. Therefore, the objective of this study was to investigate the effects of LED-Red irradiation on cardiac function in mice with HF and to reveal its mechanisms. In this study, we constructed a mouse model of HF. We found that LED-Red (630 nm) was an effective wavelength for the treatment of HF. Meanwhile, the application of LED-Red therapy to treat HF mice improved cardiac function, ameliorate heart morphology, reduced pulmonary edema, as well as inhibited collagen deposition. Moreover, LED-Red therapy attenuated the extent of perivascular fibrosis. Besides, LED-Red irradiation promoted calcium transients in cardiomyocytes as well as upregulated ATP synthesis, which may have positive implications for contractile function in mice with HF. Collectively, we identified that LED-Red exerts beneficial effects on cardiac function in HF mice possibly by promoting the synthesis of ATP.

Abstract 123: SUMO1 Modification Regulates SR Calcium ATPase Pump, SERCA2a in Heart Failure

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Changwon Kho ◽  
Ahyoung Lee ◽  
Dongtak Jeong ◽  
Jae Gyun Oh ◽  
Antoine Chaanine ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Calcium Atpase ◽  
Post Translational Modifications ◽  
Beneficial Effects ◽  
Protein Levels ◽  
In Trans ◽  
Underlying Mechanisms ◽  
Hemodynamic Performance ◽  
Reduced Activity

Background: The cardiac calcium ATPase, SERCA2a, is a critical pump responsible for Ca2+ re-uptake during excitation-contraction coupling. Impaired Ca2+ uptake resulting from decreased expression and reduced activity of SERCA2a is a hallmark of heart failure. Accordingly, restoration of SERCA2a expression by gene transfer has proved to be effective in improving cardiac function in heart-failure patients, as well as in animal models. However, the underlying mechanisms of SERCA2a’s dysfunction remain incompletely understood. Methods and Results: In this study, we show that SERCA2a is modified by SUMO1 at lysine sites 480 and 585 and that this SUMOylation is essential for preserving SERCA2a ATPase activity and stability in mouse and human cells. SUMO1 and SERCA2a SUMOylation levels were both decreased in mouse and pig models of heart failure and failing human left ventricles. To determine whether reduced SUMO1 levels are responsible for reduced SERCA2a protein levels and reduced cardiac function, we used an adenovirus associated virus-mediated gene delivery approach to up-regulate SUMO1 in trans aortic constriction-induced mouse model of heart failure. We found that increasing SUMO1 levels led to a restoration of SERCA2a levels, improved hemodynamic performance, and reduced mouse mortality. By contrast, down-regulation of SUMO1 using small hairpin RNA accelerated cardiac functional deterioration and was accompanied by decreased SERCA2a function. Conclusion: In this study, we study a new mechanism for modulation of SERCA2a activity and beneficial effects of SUMO1 in the setting of heart failure. It suggests that changes in post-translational modifications of SERCA2a could negatively affect cardiac function in heart failure. Our data may provide a new platform for the design of therapeutic strategies for heart failure.

Abstract 15315: SGLT2 Inhibitor Ertugliflozin Decreases Elevated Intracellular Sodium, Improves Myocardial Energetics and Enhances Function in Metabolic Heart Disease

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Dominique Croteau ◽  
Tomas Baka ◽  
Sara Young ◽  
Huamei He ◽  
David R Pimentel ◽  
...  
Keyword(s):  
Heart Failure ◽  
Heart Disease ◽  
Contractile Function ◽  
Control Diet ◽  
Sglt2 Inhibitor ◽  
Atp Synthesis ◽  
Intracellular Sodium ◽  
Contractile Reserve ◽  
Isolated Hearts ◽  
Metabolic Heart Disease

Background: Sodium-glucose co-transporter 2 (SGLT2) inhibitors are antidiabetic drugs of great interest in cardiology due to their improvement of heart failure outcomes independent of diabetes. As SGLT2 is not expressed in cardiomyocytes, the mechanism of such benefit remains unclear. Elevated myocardial intracellular sodium [Na + ] i has been found in heart failure and SGLT2 inhibition lowers [Na + ] i in isolated cardiomyocytes. Elevated [Na + ] i was shown to decrease mitochondrial calcium via mitochondrial Na/Ca exchanger (NCx MITO ), resulting in decreased mitochondrial ATP synthesis. We have previously shown that mice fed a diet high in fat and sugar (HFHS) develop metabolic heart disease (MHD) characterized by decreased mitochondrial ATP synthesis with decreased phosphocreatine (PCr), worsened diastolic function and contractile reserve. We hypothesize that the SGLT2 inhibitor ertugliflozin (ERTU) decreases the elevated [Na + ] i to improve energetics and contractile function in MHD. Methods and Results: Isolated hearts from mice after 6 months of HFHS vs. control diet (CD), +/- ERTU in the last month, were studied using 31 P and 23 Na NMR spectroscopy to measure PCr/ATP ratio and [Na + ] i , respectively. As expected, HFHS hearts showed lower PCr/ATP, diastolic dysfunction (↑LVEDP) and lack of contractile reserve (↓RPP) during high work protocol compared to CD hearts. Myocardial [Na + ] i was elevated more than 2-fold in HFHS compared to CD. One month of ERTU treatment decreased [Na + ] i and improved energetics and contractile function in HFHS to levels similar to or better than CD. Perfusion with CGP 37157, which inhibits NCx MITO , improved PCr/ATP in HFHS hearts. Conclusion: Lowering of myocardial [Na + ] i by ertugliflozin contributes to improved energetics and function in MHD. These results suggest targeting [Na + ] i as an effective strategy to improve cardiac dysfunction in MHD and other forms of heart disease associated with elevated myocardial [Na + ] i.

scholarly journals Impaired Myocardial Energetics Causes Mechanical Dysfunction in Decompensated Failing Hearts

Function ◽  
2020 ◽  
Vol 1 (2) ◽  
Author(s):  
Rachel Lopez ◽  
Bahador Marzban ◽  
Xin Gao ◽  
Ellen Lauinger ◽  
Françoise Van den Bergh ◽  
...  
Keyword(s):  
Heart Failure ◽  
Free Energy ◽  
Inorganic Phosphate ◽  
Contractile Function ◽  
Adenine Nucleotides ◽  
Pressure Overload ◽  
Atp Synthesis ◽  
Whole Body ◽  
Metabolic Dysfunction ◽  
Mechanical Function

Abstract Cardiac mechanical function is supported by ATP hydrolysis, which provides the chemical-free energy to drive the molecular processes underlying cardiac pumping. Physiological rates of myocardial ATP consumption require the heart to resynthesize its entire ATP pool several times per minute. In the failing heart, cardiomyocyte metabolic dysfunction leads to a reduction in the capacity for ATP synthesis and associated free energy to drive cellular processes. Yet it remains unclear if and how metabolic/energetic dysfunction that occurs during heart failure affects mechanical function of the heart. We hypothesize that changes in phosphate metabolite concentrations (ATP, ADP, inorganic phosphate) that are associated with decompensation and failure have direct roles in impeding contractile function of the myocardium in heart failure, contributing to the whole-body phenotype. To test this hypothesis, a transverse aortic constriction (TAC) rat model of pressure overload, hypertrophy, and decompensation was used to assess relationships between metrics of whole-organ pump function and myocardial energetic state. A multiscale computational model of cardiac mechanoenergetic coupling was used to identify and quantify the contribution of metabolic dysfunction to observed mechanical dysfunction. Results show an overall reduction in capacity for oxidative ATP synthesis fueled by either fatty acid or carbohydrate substrates as well as a reduction in total levels of adenine nucleotides and creatine in myocardium from TAC animals compared to sham-operated controls. Changes in phosphate metabolite levels in the TAC rats are correlated with impaired mechanical function, consistent with the overall hypothesis. Furthermore, computational analysis of myocardial metabolism and contractile dynamics predicts that increased levels of inorganic phosphate in TAC compared to control animals kinetically impair the myosin ATPase crossbridge cycle in decompensated hypertrophy/heart failure.

Beneficial effects of exercise training in heart failure are lost in male diabetic rats

2017 ◽  
Vol 123 (6) ◽  
pp. 1579-1591
Author(s):  
Dalila Boudia ◽  
Valérie Domergue ◽  
Philippe Mateo ◽  
Loubina Fazal ◽  
Mathilde Prud’homme ◽  
...  
Keyword(s):  
Heart Failure ◽  
Exercise Training ◽  
Ejection Fraction ◽  
Cardiac Function ◽  
Diabetic Rats ◽  
Diabetic Patients ◽  
Coronary Artery Ligation ◽  
Standard Diet ◽  
Beneficial Effects ◽  
Patients With Heart Failure

Exercise training has been demonstrated to have beneficial effects in patients with heart failure (HF) or diabetes. However, it is unknown whether diabetic patients with HF will benefit from exercise training. Male Wistar rats were fed either a standard (Sham, n = 53) or high-fat, high-sucrose diet ( n = 66) for 6 mo. After 2 mo of diet, the rats were already diabetic. Rats were then randomly subjected to either myocardial infarction by coronary artery ligation (MI) or sham operation. Two months later, heart failure was documented by echocardiography and animals were randomly subjected to exercise training with treadmill for an additional 8 wk or remained sedentary. At the end, rats were euthanized and tissues were assayed by RT-PCR, immunoblotting, spectrophotometry, and immunohistology. MI induced a similar decrease in ejection fraction in diabetic and lean animals but a higher premature mortality in the diabetic group. Exercise for 8 wk resulted in a higher working power developed by MI animals with diabetes and improved glycaemia but not ejection fraction or pathological phenotype. In contrast, exercise improved the ejection fraction and increased adaptive hypertrophy after MI in the lean group. Trained diabetic rats with MI were nevertheless able to develop cardiomyocyte hypertrophy but without angiogenic responses. Exercise improved stress markers and cardiac energy metabolism in lean but not diabetic-MI rats. Hence, following HF, the benefits of exercise training on cardiac function are blunted in diabetic animals. In conclusion, exercise training only improved the myocardial profile of infarcted lean rats fed the standard diet. NEW & NOTEWORTHY Exercise training is beneficial in patients with heart failure (HF) or diabetes. However, less is known of the possible benefit of exercise training for HF patients with diabetes. Using a rat model where both diabetes and MI had been induced, we showed that 2 mo after MI, 8 wk of exercise training failed to improve cardiac function and metabolism in diabetic animals in contrast to lean animals.

Carrier leakage effect on efficiency droop in InGaN/GaN light-emitting diodes

2016 ◽  
Vol 30 (20) ◽  
pp. 1650221 ◽  
Author(s):  
Yang Huang ◽  
Zhiqiang Liu ◽  
Xiaoyan Yi ◽  
Yao Guo ◽  
Shaoteng Wu ◽  
...  
Keyword(s):  
Quantum Wells ◽  
Light Emitting Diodes ◽  
Efficiency Droop ◽  
Nonradiative Recombination ◽  
Leakage Currents ◽  
Light Emitting ◽  
New Model ◽  
Leakage Effect ◽  
Text Model ◽  
The Common

A new model for efficiency droop in InGaN/GaN light-emitting diodes (LEDs) is proposed, where the primary nonradiative recombination mechanisms, including Shockley–Read–Hall (SRH), Auger and carrier leakage, are considered. A room-temperature external quantum efficiency (EQE) measurement was performed on our designed samples and analyzed by the new model. Owing to advantages over the common “[Formula: see text] model”, the “new model” is able to effectively extract recombination coefficients and calculate the leakage currents of the hole and electron. From this new model, we also found that hole leakage is distinct at low injection, while it disappears at high injection, which is contributed to the weak blocking effect of electron in quantum wells (QWs) at low injection.

Statins and myocardial remodelling: cell and molecular pathways

2011 ◽  
Vol 13 ◽  
Author(s):  
Karen E. Porter ◽  
Neil A. Turner
Keyword(s):  
Heart Failure ◽  
Molecular Mechanisms ◽  
Contractile Function ◽  
Cardiac Fibroblasts ◽  
Plasma Cholesterol ◽  
Experimental Studies ◽  
Cell Types ◽  
Small Gtpases ◽  
Cardiomyocyte Hypertrophy ◽  
Beneficial Effects

The advent of statins has revolutionised the treatment of patients with raised plasma cholesterol and increased cardiovascular risk. However, the beneficial effects of this class of drugs are far greater than would be expected from lowering of cholesterol alone, and they appear to offer cardiovascular protection at multiple levels, primarily as a result of their pleiotropic activity. Indeed, their favourable effects on the heart seem to be mediated in part through reduced prenylation and subsequent inhibition of small GTPases, particularly those of the Rho family. Such statin-mediated effects are manifested by reduced onset of heart failure and improvements in cardiac dysfunction and remodelling in heart failure patients. Experimental studies have shown that statins mediate their effects on the two major resident cell types of the heart–cardiomyocytes and cardiac fibroblasts–and thus facilitate improvement of adverse remodelling of ischaemic or non-ischaemic aetiology. This review examines evidence for the cellular effects of statins in the heart, and discusses the underlying molecular mechanisms at the level of the cardiomyocyte (hypertrophy, cell death and contractile function) and the cardiac fibroblast (differentiation, proliferation, migration and extracellular matrix synthesis). The prospects for future therapies and ongoing clinical trials are also summarised.

scholarly journals GRKs and Epac1 Interaction in Cardiac Remodeling and Heart Failure

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 154
Author(s):  
Marion Laudette ◽  
Karina Formoso ◽  
Frank Lezoualc’h
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Cardiac Remodeling ◽  
Physiological Regulation ◽  
Signaling Systems ◽  
Beneficial Effects ◽  
Sympathetic Overdrive ◽  
Β Adrenergic Receptors ◽  
G Protein Coupled ◽  
Stimulation Of

β-adrenergic receptors (β-ARs) play a major role in the physiological regulation of cardiac function through signaling routes tightly controlled by G protein-coupled receptor kinases (GRKs). Although the acute stimulation of β-ARs and the subsequent production of cyclic AMP (cAMP) have beneficial effects on cardiac function, chronic stimulation of β-ARs as observed under sympathetic overdrive promotes the development of pathological cardiac remodeling and heart failure (HF), a leading cause of mortality worldwide. This is accompanied by an alteration in cAMP compartmentalization and the activation of the exchange protein directly activated by cAMP 1 (Epac1) signaling. Among downstream signals of β-ARs, compelling evidence indicates that GRK2, GRK5, and Epac1 represent attractive therapeutic targets for cardiac disease. Here, we summarize the pathophysiological roles of GRK2, GRK5, and Epac1 in the heart. We focus on their signalosome and describe how under pathological settings, these proteins can cross-talk and are part of scaffolded nodal signaling systems that contribute to a decreased cardiac function and HF development.

Abstract 035: Mechanism of Chronic CaMKII Inhibition-Caused Regression of Heart Failure: Beneficial Effects on Neurohormonal Activation, Left Ventricular and Cardiomyocyte Contractile Function, [Ca 2 +]i Regulation and Beta-Adrenergic Modulation

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Che Ping Cheng ◽  
Qun Shao ◽  
Heng-Jie Cheng ◽  
Michael F Callahan
Keyword(s):  
Heart Failure ◽  
Contractile Function ◽  
Left Ventricular ◽  
Functional Responses ◽  
Beneficial Effects ◽  
Adrenergic Modulation ◽  
Dependent Protein ◽  
System Activation ◽  
Contraction And Relaxation ◽  
To Receive

Background: Recent evidence indicates that Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) is upregulated in heart failure (HF), contributing to electric, structural and functional remodeling. CaMKII has been proposed to be a therapeutic target for HF. However, the role and mechanism of chronic CaMKII inhibition (I) in HF is unclear. We assessed the hypothesis that CaMKII I improves cardiomyocyte function, [Ca 2+ ] i regulation, and β-adrenergic reserve, thus limiting HF progression. Methods: We compared left ventricular (LV) and myocyte functional responses and plasma levels of norepinephrine (NE) over a period of 16 weeks (W) in 6 control (C) and 14 rats with HF induced by isoproterenol (ISO) (170 mg/kg sq for 2 days). After ISO for 12 weeks, HF animals were assigned to receive 4 W treatment with: placebo (saline) (n=6), KN-93 (70 µg/kg/day sq via mini pump) (n=6), or KN-92 (70 µg/kg/day sq via pump) (n=2), respectively. Results: Compared with C, ISO-treated rats had HF onset at 4 W after ISO and progressed to severe HF at 16 W with increased plasma NE (1398 vs 342 pg/ml), decreased ejection fraction (EF, 37% vs 62%) and LV contractility (E ES , 0.8 vs 1.3 mmHg/μl). LV time constant of relaxation (τ) (17.8 vs 10.6 ms) increased, accompanied with significant reductions in cell contraction (dL/dt max , 78 vs 151 μm/s), relaxation (dR/dt max , 59 vs 114 μm/s) and [Ca 2+ ] i transient ([Ca 2+ ] iT ) (0.18 vs 0.28). HF myocyte response to β-AR stimulation (ISO, 10 -8 M) was attenuated with significantly less increases in dL/dt max (34% vs 79%) and [Ca 2+ ] iT (19% vs 36%). The LV and myocyte dysfunction persisted in KN-92-treated HF group. In contrast, treatment with KN-93 significantly increased E ES (1.2 mmHg/μl) and EF (60%), decreased τ (12.1 ms) and corrected the elevation of plasma NE (319 pg/ml). Importantly, basal myocyte contraction (dL/dt max ,147 μm/s), relaxation (dR/dt max ,107 μm/s), and [Ca 2+ ] iT (0.25) improved. ISO-induced increase in dL/dt max (71%) and [Ca 2+ ] iT (32%) were augmented and close to normal control levels. Conclusion: Chronic CaMKII I prevents HF-induced sympathetic nervous system activation and improves LV and cardiomyocyte basal and β-AR stimulated contraction and relaxation, thus playing a salutary role at later stages of HF.

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