scholarly journals In vivo effects of nitrosyl hydrogen on cardiac function and sarcoplasmic reticulum calcium pump (SERCA2a) in rats with heart failure after myocardial infarction

2020 ◽  
Vol 10 (6) ◽  
pp. 1795-1804
Author(s):  
Yanqing Guo ◽  
Jiyao Xu ◽  
Yongzhi Deng ◽  
Li Wu ◽  
Jingping Wang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Sarcoplasmic Reticulum ◽  
Cardiac Function ◽  
Calcium Pump ◽  
In Vivo Effects ◽  
Sarcoplasmic Reticulum Calcium

Influence of long-term treatment of imidapril on mortality, cardiac function, and gene expression in congestive heart failure due to myocardial infarction

2004 ◽  
Vol 82 (12) ◽  
pp. 1118-1127 ◽  
Author(s):  
Bin Ren ◽  
Qiming Shao ◽  
Pallab K Ganguly ◽  
Paramjit S Tappia ◽  
Nobuakira Takeda ◽  
...  
Keyword(s):  
Gene Expression ◽  
Myocardial Infarction ◽  
Heart Failure ◽  
Congestive Heart Failure ◽  
Sarcoplasmic Reticulum ◽  
Cardiac Function ◽  
Term Treatment ◽  
Cardiac Performance ◽  
Long Term Treatment

Although it is generally accepted that the efficacy of imidapril, an angiotensin-converting enzyme inhibitor, in congestive heart failure (CHF) is due to improvement of hemodynamic parameters, the significance of its effect on gene expression for sarcolemma (SL) and sarcoplasmic reticulum (SR) proteins has not been fully understood. In this study, we examined the effects of long-term treatment of imidapril on mortality, cardiac function, and gene expression for SL Na+/K+ ATPase and Na+–Ca2+ exchanger as well as SR Ca2+ pump ATPase, Ca2+ release channel (ryanodine receptor), phospholamban, and calsequestrin in CHF due to myocardial infarction. Heart failure subsequent to myocardial infarction was induced by occluding the left coronary artery in rats, and treatment with imidapril (1 mg·kg–1·day–1) was started orally at the end of 3 weeks after surgery and continued for 37 weeks. The animals were assessed hemody nam ically and the heart and lung were examined morphologically. Some hearts were immediately frozen at –70 °C for the isolation of RNA as well as SL and SR membranes. The mortality of imidapril-treated animals due to heart failure was 31% whereas that of the untreated heart failure group was 64%. Imidapril treatment improved cardiac performance, attenuated cardiac remodeling, and reduced morphological changes in the heart and lung. The depressed SL Na+/K+ ATPase and increased SL Na+–Ca2+ exchange activities as well as reduced SR Ca2+ pump and SR Ca2+ release activities in the failing hearts were partially prevented by imidapril. Although changes in gene expression for SL Na+/K+ ATPase isoforms as well as Na+–Ca2+ exchanger and SR phospholamban were attenuated by treatments with imidapril, no alterations in mRNA levels for SR Ca2+ pump proteins and Ca2+ release channels were seen in the untreated or treated rats with heart failure. These results suggest that the beneficial effects of imidapril in CHF may be due to improvements in cardiac performance and changes in SL gene expression.Key words: sarcolemmal Na+/K+ ATPase, Na+–Ca2+ exchange, sarcoplasmic reticulum, heart failure, ACE inhibition.

Abstract 539: Lipogenesis Regulates the Response of Cardiac Muscle to Ischemic Stress Through Sarcoplasmic Reticulum Calcium Atpase

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Larry D Spears ◽  
Babak Razani ◽  
Katsuhiko Funai ◽  
Chu Feng ◽  
Haowei Song ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Sarcoplasmic Reticulum ◽  
Calcium Homeostasis ◽  
Lipid Composition ◽  
De Novo ◽  
Phospholipid Composition ◽  
Calcium Atpase ◽  
De Novo Lipogenesis ◽  
Sarcoplasmic Reticulum Calcium

Dysfunctional calcium homeostasis is a hallmark of heart failure, a sequela of myocardial infarction (MI). Previous research has shown that mice deficient in cardiac fatty acid synthase (FAS), the rate-limiting enzyme for de novo lipogenesis, have dysfunctional calcium signaling and a predisposition to heart failure. Yet the mechanisms linking endogenous lipid synthesis, myocardial calcium homeostasis, and cardiac function remain poorly understood. A major step in calcium handling is the transport of cytosolic calcium back into the sarcoplasmic reticulum (SR) by sarcoplasmic reticulum calcium ATPase (SERCA), and recent evidence suggests that SR lipid composition can affect SERCA function. To determine whether FAS plays a role in SERCA activity in the heart, we evaluated FASKard ( FAS K nockout in the Myoc ard ium) mice in the setting of experimental myocardial infarction (MI). Deletion of heart FAS caused a decrease in SERCA activity in younger adult (4 months) and aged (12 months) mice when compared to control (Ctrl) mice of the same age. Lipidomic analysis of the SR showed the reduced SERCA activity in FASKard mice was due to an altered SR phospholipid composition, leading to an imbalance of SR phosphatidylcholine to phosphatidylethanolamine phospholipid ratios. This altered ratio of SR phospholipids was due to a decrease in the abundance of specific phosphatidylethanolamine phospholipid species. MI caused a decrease in SERCA activity in both Ctrl and FASKard mice hearts. FASKard mice after MI had impaired survival with concomitantly decreased SERCA activity compared to Ctrl mice after MI. FASKard MI mice also had a perturbed ratio of SR phosphatidylcholine to phosphatidylethanolamine phospholipids compared to Ctrl MI mice, due to a decrease in certain phosphatidylethanolamine phospholipids. Additionally, MI induced FAS expression in the myocardium. These findings suggest that myocardial de novo lipogenesis is critical to the maintenance of the SR phospholipid composition, SR-mediated calcium homeostasis, and blunting the development of heart failure, particularly ischemic cardiomyopathy. Furthermore, FAS regulation of the SR lipid composition represents a novel therapeutic strategy in the treatment of heart failure.

scholarly journals Negative feedback of SNRK to circ-SNRK regulates cardiac function post-myocardial infarction

2021 ◽  
Author(s):  
Zhi-Yan Wang ◽  
Xiao-Xiao Liu ◽  
Yun-Fei Deng
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Cardiac Function ◽  
Negative Feedback ◽  
Atp Synthesis ◽  
Protective Role ◽  
Splicing Regulator ◽  
Mitochondrial Efficiency

AbstractA limited delivery of oxygen and metabolic substrate to the heart caused by myocardial infarction (MI) impairs the cardiac function, and often results in heart failure. Here, we identified a circRNA (circ-SNRK) from SNRK (sucrose nonfermenting 1-related kinase, which can increase the cardiac mitochondrial efficiency) in cardiomyocytes (CMs). Circ-SNRK can sponge the miR-33 and in turn improved the ATP synthesis via SNRK, proving the existence of circ-SNRK - miR-33 - SNRK axis. Furthermore, we found that protein NOVA1 (NOVA alternative splicing regulator 1) could accelerate the circ-SNRK formation; a cleaved peptide (~55 kDa) from SNRK enters the nucleus and blocks the cyclization of circ-SNRK via binding to NOVA1. The aforementioned negative feedback of SNRK to circ-SNRK limited the SNRK at a proper level, and inhibited the protective role of circ-SNRK in ischemic heart. In addition, our in vivo experiment indicated that the overexpression of exogenic circ-SNRK could break this loop and improves the cardiac function post-MI in rats. Together, our results demonstrated that the negative loop of circ-SNRK with SNRK regulates the energy metabolism in CMs, thus might be a potential therapeutic target for heart failure.

Abstract 295: Enhanced Cardiac Function And Lower Circulating Aldosterone Levels In βArrestin1 Knockout Mice During Post-myocardial Infarction Heart Failure Progression

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Anastasios Lymperopoulos ◽  
Giuseppe Rengo ◽  
Erhe Gao ◽  
Ashley Siryk ◽  
Samalia Dabul ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Cardiac Function ◽  
Underlying Mechanism ◽  
Post Myocardial Infarction ◽  
Aldosterone Production ◽  
Heart Failure Progression ◽  
Adverse Remodeling ◽  
And Function

Introduction: Chronic heart failure (HF) is characterized by enhanced circulating cardiotoxic hormones, among the most prominent of which is aldosterone, which contributes to the increased morbidity and mortality of the disease by promoting cardiac adverse remodeling post-myocardial infarction (MI). Cardiac β-adrenergic receptor (ΑR) desensitization and downregulation are a hallmark abnormality in HF at the molecular level and are due to the concerted action of cardiac G protein-coupled receptor kinase-2 (GRK2), together with its co-factors in receptor desensitization, the βarrestins (βarrs). We have also recently established that βarr1 promotes angiotensin II-dependent aldosterone production in the adrenal cortex, and this leads to elevated circulating aldosterone levels in vivo, both under normal conditions and during post-MI HF progression. Hypothesis: Herein, we sought to investigate the effects of genetically deleting βarr1 on post-MI cardiac function and hyperaldosteronic status in mice progressing to HF. Methods: We uitilized the βarr1KO mouse model and studied these mice at 4 weeks after surgically induced MI, in parallel with C57/B6 wild type (WT) controls. Cardiac function was assessed by echocardiography and in vivo catheterization. Plasma aldosterone was measured by ELISA. Results: Cardiac function is markedly improved in βarr1KO`s at 4 weeks post-MI, as evidenced by increased ejection fraction compared to WT mice (41.5 + 2.8 % vs. 21.8 + 2.4 %, respectively, n=9, p<0.0001) and increased isoproterenol-induced contractility. Additionally, cardiac dimensions are significantly reduced compared to WT`s, indicating attenuation of adverse cardiac remodeling. Importantly, plasma circulating aldosterone levels are significantly lowered and cardiac βAR signaling and function appear elevated in post-MI βarr1KO`s compared to control WT`s. Conclusions: Genetic deletion of βarr1 substantially improves cardiac function, adverse remodeling, hyperaldosteronism, and cardiac βAR function during post-MI HF progression. The underlying mechanism is attenuation of both cardiac βAR desensitization/downregulation and adrenal aldosterone production, which is βarr1-dependent.

scholarly journals Author Correction: In vivo transduction of ETV2 improves cardiac function and induces vascular regeneration following myocardial infarction

2019 ◽  
Vol 51 (9) ◽  
pp. 1-1 ◽  
Author(s):  
Sunghun Lee ◽  
Dong Hun Lee ◽  
Bong-Woo Park ◽  
Ri Youn Kim ◽  
Anh Duc Hoang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Vascular Regeneration

scholarly journals p90 ribosomal S6 kinase 3 contributes to cardiac insufficiency in α-tropomyosin Glu180Gly transgenic mice

2013 ◽  
Vol 305 (7) ◽  
pp. H1010-H1019 ◽  
Author(s):  
Catherine L. Passariello ◽  
Marjorie Gayanilo ◽  
Michael D. Kritzer ◽  
Hrishikesh Thakur ◽  
Zoharit Cozacov ◽  
...  
Keyword(s):  
Heart Failure ◽  
Transgenic Mice ◽  
Cardiac Function ◽  
Interstitial Fibrosis ◽  
Cardiac Insufficiency ◽  
S6 Kinase ◽  
Transgenic Expression ◽  
P90 Ribosomal S6 Kinase ◽  
Ribosomal S6 Kinase

Myocardial interstitial fibrosis is an important contributor to the development of heart failure. Type 3 p90 ribosomal S6 kinase (RSK3) was recently shown to be required for concentric myocyte hypertrophy under in vivo pathological conditions. However, the role of RSK family members in myocardial fibrosis remains uninvestigated. Transgenic expression of α-tropomyosin containing a Glu180Gly mutation (TM180) in mice of a mixed C57BL/6:FVB/N background induces a cardiomyopathy characterized by a small left ventricle, interstitial fibrosis, and diminished systolic and diastolic function. Using this mouse model, we now show that RSK3 is required for the induction of interstitial fibrosis in vivo. TM180 transgenic mice were crossed to RSK3 constitutive knockout ( RSK3−/−) mice. Although RSK3 knockout did not affect myocyte growth, the decreased cardiac function and mild pulmonary edema associated with the TM180 transgene were attenuated by RSK3 knockout. The improved cardiac function was consistent with reduced interstitial fibrosis in the TM180; RSK3−/− mice as shown by histology and gene expression analysis, including the decreased expression of collagens. The specific inhibition of RSK3 should be considered as a potential novel therapeutic strategy for improving cardiac function and the prevention of sudden cardiac death in diseases in which interstitial fibrosis contributes to the development of heart failure.

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