44 Beneficial effects of pharmacological enhancement of the endothelial NO synthases on cardiac function and hypertrophy in an animal model of heart failure despite normal EF

2007 ◽  
Vol 6 (1) ◽  
pp. 4-4
Author(s):  
D WESTERMANN ◽  
S JAEGER ◽  
A RIAD ◽  
U RICHTER ◽  
H SCHULTHEISS ◽  
...  
Keyword(s):  
Heart Failure ◽  
Animal Model ◽  
Cardiac Function ◽  
Beneficial Effects

SUMO-1 Gene Transfer Improves Cardiac Function in a Large-Animal Model of Heart Failure

2013 ◽  
Vol 5 (211) ◽  
pp. 211ra159-211ra159 ◽  
Author(s):  
L. Tilemann ◽  
A. Lee ◽  
K. Ishikawa ◽  
J. Aguero ◽  
K. Rapti ◽  
...  
Keyword(s):  
Heart Failure ◽  
Animal Model ◽  
Gene Transfer ◽  
Cardiac Function ◽  
Large Animal Model ◽  
Large Animal

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.

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.

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.

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 567: Ivabradine Improved Cardiac Function, Fibrosis And Hyperexcitability In Rat Post-myocardial Infarction Severe Heart Failure.

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Paul Milliez ◽  
Johnny Nehme ◽  
Estelle Robidel ◽  
Camille Rodriguez ◽  
JaneLise Samuel ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Sinus Node ◽  
Severe Heart Failure ◽  
Lv Function ◽  
Coronary Artery Ligation ◽  
Artery Ligation ◽  
Adult Rats ◽  
Beneficial Effects ◽  
Lv Dysfunction

The selective sinus node I f current inhibitor Ivabradine (Iva) reduces heart rate (HR) without any other hemodynamic effects. We investigated in a rat model of post-MI severe heart failure, the effects of a chronic Iva administration on LV function, structure and electrical remodelling. Methods . MI was induced by coronary artery ligation in adult rats: echocardiography and Holter ECG were performed 2 months (m) after MI i.e. before randomization (n=12/group) into MI and MI+Iva (10 mg/kg/d) groups, and 3 m later. In ventricles, collagen was quantified after Sirius red staining of section and ACE and AT1-receptor mRNA expression (normalized to GAPDH) was assayed by RT-PCR. Results : 2m-post MI, all rats displayed severe decreased LVEF, and increased LVEDP compared to sham-operated (28%±3 vs 66%±5 and 32±2 vs 10±1 mmHg, respectively; p<0.05). In 5m-post-MI, LVEF and LVEDP were stabilized with Iva (31±1% and 24±2 mmHg), while they were worsened in MI groups (21±3% and 38±2mmHg). Blood pressure, body and heart weights were similar in MI and MI+Iva. Iva reduced HR (RR: 201±5 vs 179±3 ms in MI; p<0.05) and ventricular premature beats (514±152 vs 4717±1363/day for MI; p<0.05), and improved HR variability (SDRR: 5±1.5 vs 3.9± 0.6 for MI; p<0.05). There were no effects of Iva on duration (ms) of PR (45±3 vs 44±3), QRS (51±3 vs 46±3) and QT (106±7 vs 99±6, for MI and MI+Iva, respectively). The increased ventricular collagen in MI (4.0±0.1 vs 0.8±0.2 % in sham; p<0.05) was markedly reduced in MI+Iva (1.8±0.1%, p<0.0001 vs MI). The increases in ventricular gene expression of ACE and AT-1 receptor in MI rats (2.5 and 6 folds versus sham operated, respectively, p<0.05) were completely blunted by Iva treatment. Conclusion: Iva treatment of the post-MI heart failure: 1- markedly reduced HR and ventricular excitability and without harmful effects on conduction; 2- prevented worsening of LV dysfunction and remodelling, and 3- induced a downregulation of cardiac RAAS transcripts. Thus, through its negative chronotropic effects, Iva allowed the maintenance of cardiac function below the threshold for a tissular RAAS stimulation even in severe post-MI cardiac failure. Such beneficial effects of Iva on cardiac remodelling open new perspectives for the treatment of severe heart failure

Beneficial effects of melatonin in juvenile rats with heart failure

2019 ◽  
Author(s):  
Yao Wu ◽  
Feifei Si ◽  
Li Luo ◽  
Fengchuan Jing ◽  
Kunfeng Jiang ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Sham Group ◽  
Ventricular Dysfunction ◽  
Protective Role ◽  
Aortic Constriction ◽  
Juvenile Rats ◽  
Beneficial Effects ◽  
Abdominal Aortic

Abstract Background: Adult rodent studies showed that melatonin is very effective in treatment of ameliorating cardiovascular disease. Melatonin is also able to reduce cardiac hypertrophy and heart failure (HF) in juvenile rodents. Here, we study the effect of melatonin on the cardiac function of juvenile rats with HF. Methods: Juvenile rats with HF were induced by abdominal aortic constriction (AAC). Sham-operated rats were established in parallel. Five weeks after the surgery, rats with ventricular dysfunction were randomly divided into two groups: the treatment group was injected with melatonin (10 mg/kg/d, intraperitoneal injection), and the HF group was injected with placebo. Simultaneously, placebo was administered to the sham group. Results: After administration for 4 weeks, the treated rats did not exhibit a decline in cardiac function as assessed by echocardiography analysis. Moreover, the increase in expression of ANP, BNP, caspase-1, IL-1β, bax, CaMKII, PLN, and RyR2 was markedly blunted by melatonin, while the decrease in expression of bcl-2 was improved in the melatonin treated rats. Conclusions: Our findings support a protective role of melatonin in cardiomyocytes, at least in part via reducing cardiac pyroptosis, apoptosis and remaining calcium homeostasis.

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