Heart failure and the glutathione cycle: an integrated view

2020 ◽  
Vol 477 (17) ◽  
pp. 3123-3130
Author(s):  
Anand K. Bachhawat ◽  
Shambhu Yadav ◽  
Ashwin K. Jainarayanan ◽  
Pratiksha Dubey
Keyword(s):  
Heart Failure ◽  
Cellular Response ◽  
Short Review ◽  
Signaling Mechanism ◽  
Developing Heart ◽  
The Family ◽  
Glutathione Cycle ◽  
Fetal Reprogramming ◽  
Contraction And Relaxation

Heart failure results from the heart's inability to carryout ventricular contraction and relaxation, and has now become a worldwide problem. During the onset of heart failure, several signatures are observed in cardiomyocytes that includes fetal reprogramming of gene expression where adult genes are repressed and fetal genes turned on, endoplasmic reticulum stress and oxidative stress. In this short review and analysis, we examine these different phenomenon from the viewpoint of the glutathione cycle and the role of the recently discovered Chac1 enzyme. Chac1, which belongs to the family of γ-glutamylcyclotransferases, is a recently discovered member of the glutathione cycle, being involved in the cytosolic degradation of glutathione. This enzyme is induced during the Endoplasmic Stress response, but also in the developing heart. Owing to its exclusive action on reduced glutathione, its induction leads to an increase in the oxidative redox potential of the cell that also serves as signaling mechanism for calcium ions channel activation. The end product of Chac1 action is 5-oxoproline, and studies with 5-oxoprolinase (OPLAH), an enzyme of the glutathione cycle has revealed that down-regulation of OPLAH can lead to the accumulation of 5-oxproline which is an important factor in heart failure. With these recent findings, we have re-examined the roles and regulation of the enzymes in the glutathione cycle which are central to these responses. We present an integrated view of the glutathione cycle in the cellular response to heart failure.

The effect of oestrogen withdrawal on cardiac Ca2+ regulation and the influence of GPER1

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A.J Francis ◽  
J.M Firth ◽  
N Islam ◽  
J Gorelik ◽  
K.T MacLeod
Keyword(s):  
Heart Failure ◽  
Structural Integrity ◽  
Left Ventricular ◽  
Funding Source ◽  
Hormonal Changes ◽  
Ion Conductance ◽  
Developing Heart ◽  
Rapid Stimulation ◽  
Post Menopausal

Abstract Background Post-menopausal women have an enhanced risk of developing heart failure, attributed to declining oestrogen levels during menopause. However, the signalling mechanisms remain undetermined. Purpose We aim to determine the role of G-protein coupled oestrogenic receptor 1 (GPER1) in intracellular Ca2+ regulation and the consequences of hormonal changes that may exacerbate the pathophysiology of heart failure. Methods Ovariectomy (OVx) (mimics menopausal hormone changes) or sham surgeries were conducted on female guinea pigs. Left ventricular cardiomyocytes were isolated 150-days post-operatively for experimental use. Cellular t-tubule network and structural integrity was measured using fluorescent di-8-ANEPPs staining and scanning ion conductance microscopy. GPER1 expression and localisation was measured by Western blot and immunostaining. The role of GPER1 activation was measured using selective agonist G-1 in electrophysiological and Ca2+-sensitive dye fluorescence experiments. Results Following oestrogen withdrawal, the t-tubule network density decreased by 13% and z-groove index reduced by 15%. GPER1 predominantly localised to the peri-nuclear endoplasmic reticulum and its expression increased by 32% in OVx. Action potential duration (APD) prolonged in OVx and following GPER1 activation, APD90 shortened by 11% and 25% in sham and OVx respectively. OVx cells had larger peak inward Ca2+ current (ICaL) (by 22%) and sarcoplasmic reticulum (SR) Ca2+ content (by 13%), compared with sham. While GPER1 activation had little effect on peak ICaL or SR content, it reduced Ca2+ transient amplitude (by 20%), SR fractional release (by 11%) in OVx cells. The frequency of occurrence of spontaneous Ca2+ waves evoked by periods of rapid stimulation reduced by 40% and wave-free survival time prolonged in OVx cells following GPER1 activation. Conclusions In the hearts of an animal species whose electrophysiology and intracellular Ca2+ regulation is akin to humans, we show that following oestrogen deficiency, the t-tubule network is down-regulated and becomes disorganised, GPER1 expression is increased and its activation induces negative inotropic responses in cardiomyocytes. This may limit the adverse changes to Ca2+ signalling reported in OVx that could be pro-arrhythmic and exacerbate the progression to heart failure. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): British Heart Foundation

scholarly journals MicroRNAs as Biomarkers and Therapeutic Targets in Heart Failure

2019 ◽  
Vol 65 (3) ◽  
pp. 77-79
Author(s):  
István Adorján Szabó ◽  
Atilla Frigy
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Messenger Rna ◽  
Short Review ◽  
Rna Molecules ◽  
Functional Changes ◽  
Diagnosis And Prognosis ◽  
Adaptive Processes ◽  
Altered Gene

AbstractHeart failure still represents a real challenge both in everyday practice and research, due to the complex issues related to its pathogenesis and management. Humoral biomarkers have emerged in the last decades as useful tools in the diagnosis, risk stratification and guiding the treatment of heart failure. These molecules are related to different pathological and adaptive processes, like myocardial injury, neurohormonal activation and cardiac remodeling, their most widespread representatives being the natriuretic peptides (e.g. NT-proBNP). The role of altered gene expression and transcription as the basis of myocardial structural and functional changes in heart failure is largely recognized. MicroRNAs (miRNAs) are non-coding RNAs which have a major role in post-transcriptional gene expression by interfering with messenger RNA molecules. Our short review summarizes the molecular biology of miRNAs and their possible role as biomarkers in the diagnosis and prognosis of heart failure. Furthermore, the therapeutical perspectives conferred by these molecules are also presented.

scholarly journals The Role of Galectin-3 and ST2 in Cardiology: A Short Review

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1167
Author(s):  
Ana Merino-Merino ◽  
Jeronimo Gonzalez-Bernal ◽  
Dario Fernandez-Zoppino ◽  
Ruth Saez-Maleta ◽  
Jose-Angel Perez-Rivera
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Coronary Heart Disease ◽  
Cardiac Remodeling ◽  
Short Review ◽  
Cardiac Diseases ◽  
Myocardial Cells ◽  
Prognostic Role ◽  
Galectin 3

Galectin-3 is a lectin that binds beta-galactosides. It is involved in cardiac remodeling and fibrosis through the activation of macrophages and fibroblasts. ST2 is secreted by myocardial cells due to cardiac overload. These two biomarkers have been traditionally studied in the field of heart failure to guide medical therapy and detect the progression of the disease. Nevertheless, there are novel evidences that connect galectin-3 and ST2 with coronary heart disease and, specifically, with atrial fibrillation. The aim of this article is to concisely review the diagnostic and prognostic role of galectin-3 and ST2 in different cardiac diseases.

1178Unsuspected role of the cardiac PKA type I in excitation-contraction coupling and in heart failure development

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Gandon-Renard ◽  
I Bedioune ◽  
S Karam ◽  
A Varin ◽  
P Lechene ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ex Vivo ◽  
Cardiac Contractility ◽  
Cardiac Contraction ◽  
Type I ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Contraction And Relaxation

Abstract The cAMP-dependent protein kinase (PKA) consists of two regulatory (R) and two catalytic (C) subunits and comprises two subtypes, PKAI and PKAII, defined by the nature of their regulatory subunits, RIα and RIIα respectively. Whereas PKAII is thought to play a key role in β-adrenergic (β-AR) regulation of cardiac contractility, the function of PKAI is unclear. To address this question, we generated mice with cardiomyocyte-specific and conditional invalidation of the RIα subunit of PKA. Tamoxifen injection in 8 weeks-old mice resulted in a >70% decrease in RIα protein without modification of other PKA subunits, which was associated with ∼2-fold increased basal PKA activity in RIα-KO mice (p<0.05, N=6/group). This translated into enhanced cardiac contraction and relaxation, as observed in vivo by increased fractional shortening and E-wave velocity (p<0.05, N=10/group) and ex vivo by increased LV pressure and maximal rate of contraction and relaxation (p<0.05, N=9/group). L-type Ca2+ current density was increased in ventricular myocytes from RIα-KO, and β-AR stimulation was decreased by ∼50% (p<0.05, n=38 cells for WT, and, n=40 for RIα-KO). Consistently, Ca2+ transients amplitude and relaxation kinetics were increased, along with increased occurrence of Ca2+ sparks and waves (p<0.05, n=44 cells for WT, and, n=50 for RIα KO). Phosphorylation of Ca2+ channels (CaV1.2), PLB, RyR2 and cMyBP-C at PKA sites was increased >2-fold (p<0.05, N=6/group) in RIα KO without modification of total protein expression. With age, these mice developed a congestive heart failure (HF) phenotype with massive hypertrophy and fibrosis which eventually led to death in 50% of RIα-KO mice at 50 weeks (versus 0% in WT, p<0.01). These results reveal a previously unsuspected role of PKA type I in cardiac excitation-contraction coupling and HF.

scholarly journals The role of correction of anaemia in patients with congestive heart failure: A short review

2008 ◽  
Vol 10 (9) ◽  
pp. 819-823 ◽  
Author(s):  
Donald S. Silverberg ◽  
Dov Wexlerb ◽  
Adrian Iaina ◽  
Doron Schwartz
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Short Review

scholarly journals Role of Family in Increasing Self Efficacy Patient Heart Failure

2020 ◽  
Vol 8 (4) ◽  
pp. 435
Author(s):  
Suwardha Yunus ◽  
Ariyanti Saleh ◽  
Takdir Tahir
Keyword(s):  
Heart Failure ◽  
Self Efficacy ◽  
Self Care ◽  
The Self ◽  
Mortality And Morbidity ◽  
The Family ◽  
Structural Abnormalities ◽  
Life Threatening

Heart failure is a collection of clinical and complex problems that can be life-threatening due to structural abnormalities or heart dysfunction. In both developed and developing countries. The role of the family is needed in the handling of HF patients to prevent the occurrence of mortality and morbidity, also has an impact on self-efficacy. This review identifies the role of the family in increasing self-efficacy. Metode of discursive with a literature review of several articles related to the 2010-2019 scientific search using PubMed, Cochran, ScienceDirect, google scholar, there are 117 articles. Article exclusion is not in English and not in full text. The remaining 36 articles are. The inclusion of articles according to the study were 5 articles. Results are obtained 5 articles consisting of 1 article discussing the role of the family as caregivers for self-care, 2 articles discuss increasing the self-efficacy of HF patients and their treatment. And 2 articles discuss the role of the family as a supporter of HRQoL. The role of the family in the care of patients with HF as caregivers fulfills the patient's self-care, and affect the patient's self-efficacy to improve the quality of life.

POPDC proteins and cardiac function

2019 ◽  
Vol 47 (5) ◽  
pp. 1393-1404 ◽  
Author(s):  
Thomas Brand
Keyword(s):  
Potential Role ◽  
Striated Muscle ◽  
Short Review ◽  
Effector Proteins ◽  
Muscle Disease ◽  
Disease Genes ◽  
Protein Protein Interaction ◽  
Interaction Partners ◽  
And Function

Abstract The Popeye domain-containing gene family encodes a novel class of cAMP effector proteins in striated muscle tissue. In this short review, we first introduce the protein family and discuss their structure and function with an emphasis on their role in cyclic AMP signalling. Another focus of this review is the recently discovered role of POPDC genes as striated muscle disease genes, which have been associated with cardiac arrhythmia and muscular dystrophy. The pathological phenotypes observed in patients will be compared with phenotypes present in null and knockin mutations in zebrafish and mouse. A number of protein–protein interaction partners have been discovered and the potential role of POPDC proteins to control the subcellular localization and function of these interacting proteins will be discussed. Finally, we outline several areas, where research is urgently needed.

Protective role of peroxiredoxin-4 in heart failure

2020 ◽  
Vol 134 (1) ◽  
pp. 71-72
Author(s):  
Naseer Ahmed ◽  
Masooma Naseem ◽  
Javeria Farooq
Keyword(s):  
Heart Failure ◽  
Cardiac Fibroblasts ◽  
Protective Role ◽  
Oxidative Stress Markers ◽  
Stress Markers ◽  
Total Antioxidant ◽  
Galectin 3 ◽  
Consequent Increase ◽  
And Oxidative Stress

Abstract Recently, we have read with great interest the article published by Ibarrola et al. (Clin. Sci. (Lond.) (2018) 132, 1471–1485), which used proteomics and immunodetection methods to show that Galectin-3 (Gal-3) down-regulated the antioxidant peroxiredoxin-4 (Prx-4) in cardiac fibroblasts. Authors concluded that ‘antioxidant activity of Prx-4 had been identified as a protein down-regulated by Gal-3. Moreover, Gal-3 induced a decrease in total antioxidant capacity which resulted in a consequent increase in peroxide levels and oxidative stress markers in cardiac fibroblasts.’ We would like to point out some results stated in the article that need further investigation and more detailed discussion to clarify certain factors involved in the protective role of Prx-4 in heart failure.

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