scholarly journals Iron Deficiency as a Therapeutic Target in Cardiovascular Disease

2019 ◽  
Vol 12 (3) ◽  
pp. 125 ◽  
Author(s):  
Samira Lakhal-Littleton
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Chronic Heart Failure ◽  
Iron Deficiency ◽  
Iron Supplementation ◽  
Iron Homeostasis ◽  
Iron Regulatory Proteins ◽  
Cellular Iron ◽  
Cellular Iron Homeostasis

Iron deficiency is the most common nutritional disorder in the world. It is prevalent amongst patients with cardiovascular disease, in whom it is associated with worse clinical outcomes. The benefits of iron supplementation have been established in chronic heart failure, but data on their effectiveness in other cardiovascular diseases are lacking or conflicting. Realising the potential of iron therapies in cardiovascular disease requires understanding of the mechanisms through which iron deficiency affects cardiovascular function, and the cell types in which such mechanisms operate. That understanding has been enhanced by recent insights into the roles of hepcidin and iron regulatory proteins (IRPs) in cellular iron homeostasis within cardiovascular cells. These studies identify intracellular iron deficiency within the cardiovascular tissue as an important contributor to the disease process, and present novel therapeutic strategies based on targeting the machinery of cellular iron homeostasis rather than direct iron supplementation. This review discusses these new insights and their wider implications for the treatment of cardiovascular diseases, focusing on two disease conditions: chronic heart failure and pulmonary arterial hypertension.

Overexpression of mitochondrial ferritin causes cytosolic iron depletion and changes cellular iron homeostasis

Blood ◽  
2005 ◽  
Vol 105 (5) ◽  
pp. 2161-2167 ◽  
Author(s):  
Guangjun Nie ◽  
Alex D. Sheftel ◽  
Sangwon F. Kim ◽  
Prem Ponka
Keyword(s):  
Iron Homeostasis ◽  
Rna Binding ◽  
Binding Activity ◽  
Intracellular Iron ◽  
Free Radical Damage ◽  
Iron Regulatory Proteins ◽  
Cellular Iron ◽  
Cellular Iron Uptake ◽  
A Cell ◽  
Cellular Iron Homeostasis

AbstractCytosolic ferritin sequesters and stores iron and, consequently, protects cells against iron-mediated free radical damage. However, the function of the newly discovered mitochondrial ferritin (MtFt) is unknown. To examine the role of MtFt in cellular iron metabolism, we established a cell line that stably overexpresses mouse MtFt under the control of a tetracycline-responsive promoter. The overexpression of MtFt caused a dose-dependent iron deficiency in the cytosol that was revealed by increased RNA-binding activity of iron regulatory proteins (IRPs) along with an increase in transferrin receptor levels and decrease in cytosolic ferritin. Consequently, the induction of MtFt resulted in a dramatic increase in cellular iron uptake from transferrin, most of which was incorporated into MtFt. The induction of MtFt caused a shift of iron from cytosolic ferritin to MtFt. In addition, iron inserted into MtFt was less available for chelation than that in cytosolic ferritin and the expression of MtFt was associated with decreased mitochondrial and cytosolic aconitase activities, the latter being consistent with the increase in IRP-binding activity. In conclusion, our results indicate that overexpression of MtFt causes a dramatic change in intracellular iron homeostasis and that shunting iron to MtFt likely limits its availability for active iron proteins.

Calcein and the Labile Iron Pool.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1546-1546
Author(s):  
Shan Soe-Lin ◽  
Joan L. Buss ◽  
Evelyn Tang ◽  
Prem Ponka
Keyword(s):  
Iron Homeostasis ◽  
Iron Chelator ◽  
Acetoxymethyl Ester ◽  
Iron Regulatory Proteins ◽  
Labile Iron Pool ◽  
Cellular Iron ◽  
Labile Iron ◽  
The Difference ◽  
Iron Pool ◽  
Cellular Iron Homeostasis

Abstract The labile iron pool is a putative cytosolic compartment of loosely bound, redox-active, chelator-accessible iron. Iron contained within this pool is thought to influence the activity of iron regulatory proteins (IRPs), which bind to iron response elements (IRE) during low iron conditions; this association blocks the translation of ferritin mRNA, and stabilizes transferrin receptor mRNA. High levels of labile iron have been shown to promote oxidative stress. As this pool has such profound effects upon cellular iron homeostasis, there has been great interest in the development of methods to measure labile iron. Calcein, a fluorescent iron chelator, has been widely used to monitor the labile iron pool. When the non-fluorescent acetoxymethyl ester moiety (calcein-AM), enters cells, it is immediately cleaved by cytosolic esterases to its cell-impermeable, fluorescent calcein form. Iron binding to calcein quenches its fluorescence, which can subsequently be recovered following the loss of its iron to a stronger chelator. The difference in fluorescence between the bound and unbound calcein forms is thought to be proportional to the labile iron pool itself. While this method has been commonly exploited, it is unknown whether calcein may over-estimate the size of the labile pool by stripping iron from sources where it may be loosely bound, or by intercepting iron during its passage from one compartment to another. Although it is believed that calcein exerts very little direct influence on cellular iron homeostasis and acts only as a passive sensor of labile iron, some recent evidence from our lab indicates that this may not be the case. We have observed that incubation with calcein results in the activation of IRP-2 and stabilization of HIF-1α, a potent physiological regulator governing the expression of genes involved in oxygen sensing and iron metabolism. Furthermore, we have found that the size of the labile iron pool as measured by calcein was proportional to the amount of calcein loaded in HeLa and K562 cell lines. These findings suggest that calcein may be able to perturb cellular iron homeostasis, and may not accurately reflect the size of the labile iron pool. While calcein may still be used for comparative purposes under identically controlled conditions, its usefulness as a quantifying agent should be regarded with caution.

scholarly journals Endokrinnye mekhanizmy modulyatsii serdechnoydeyatel'nosti u patsientov s khronicheskoyserdechnoy nedostatochnost'yu: rol' gormona rosta

2010 ◽  
Vol 7 (4) ◽  
pp. 4-7
Author(s):  
I I Dedov ◽  
I Z Bondarenko ◽  
O B Bezlepkina
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Growth Hormone ◽  
Cardiovascular Diseases ◽  
Chronic Heart Failure ◽  
Life Expectancy ◽  
Sudden Death

Chronic heart failure (CHF) is a complication of most cardiovascular diseases. Despite of the last achievements in pharmacotherapy, life expectancy in patients with CHF remains to be the lowest, and the risk of sudden death is the highest. The last 20 years stressed the importance of growth hormone role in the development of cardiovascular disease, and its potential in treatment of terminal CHF. This article reviews the most well-known research conducted in this area.

scholarly journals A modern view of the place of b-blockers in the treatmentof cardiovascular disease: the choice of drug within a class is crucial

2015 ◽  
Vol 12 (4) ◽  
pp. 69-74
Author(s):  
O D Ostroumova ◽  
V M Fomina ◽  
E A Smolyarchuk
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Cardiovascular Diseases ◽  
Chronic Heart Failure ◽  
Arterial Hypertension ◽  
Clinical Studies ◽  
Metoprolol Succinate ◽  
Selection Of

In the article discusses questions of application of b-blockers (b-AB) for the treatment of arterial hypertension, coronary heart disease, chronic heart failure. The data from modern Russian and European recommendations about the place of b-AB in the treatment of cardiovascular diseases. Analyzed in detail the selection of b-AB inside the class from the standpoint of pharmacokinetics, selectivity, study in clinical studies. Data about efficiency and safety of application of metoprolol succinate for the treatment of arterial hypertension, coronary heart disease, chronic heart failure.

scholarly journals The ST2 diagnostic value in selection of patients for heart transplantation and post-transplant period

2019 ◽  
Vol 40 (1) ◽  
pp. 4-11
Author(s):  
A. S. Nikonenko ◽  
O. O. Tanska
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Chronic Heart Failure ◽  
Heart Transplantation ◽  
Prognostic Value ◽  
Clinical Manifestations ◽  
Mechanical Damage ◽  
Risk Of Death ◽  
Diagnostic And Prognostic Value

Purpose of the study. Study ST2 diagnostic marker in the development and severity of heart failure, evaluation of transplant status and the risk of developing a rejection crisis, as well as the risk of death in patients with cardiovascular disease.Material and methods. There were 41 patients under observation. The cases were conventionally divided into two groups: the first group of patients with chronic heart failure (n = 28), and the control group who performed orthotopic transplantation of the heart (n = 13).Results and discussion. These results suggest that ST2 is a real marker of chronic heart failure or a good predictor of mortality in decompensated patients. Changes in ST2 levels in patients after orthotopic cardiac transplantation may be potentially useful in detecting acute cellular rejection, as well as in controlling rejection therapy. The article is devoted to the analysis of the prognostic role of the ST2 biomarker in the pre and post-transplantation period. ST2 is one of the most promising diagnostic markers for the development and severity of heart failure, as well as the risk of death in patients with cardiovascular disease. ST2 is expressed in cardiomyocytes in response to pathological processes and various mechanical damage in the heart, which allows to diagnose cardiovascular diseases even before clinical manifestations. It is likely that ST2 level measurement of heart transplantation may have a diagnostic and prognostic value when evaluating the graft state and the risk of developing rejection.Conclusions. ST2 is one of the most promising diagnostic markers of development and severity of heart failure, as well as the risk of death in patients with cardiovascular disease. ST2 is expressed in cardiomyocytes in response to pathological processes and various mechanical damage in the heart, which allows to diagnose cardiovascular diseases even before clinical manifestations. Measuring the level of ST2 for heart transplantation may have a diagnostic and prognostic value in evaluating the condition of the graft and the risk of developing rejection. Keywords:heart failure, ST2, heart transplantation, rejection crisis.

Cardiac and vascular ageing

2017 ◽  
pp. 729-736
Author(s):  
Hidetaka Ota ◽  
Masahiro Akishita
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Chronic Heart Failure ◽  
Left Ventricular Hypertrophy ◽  
Blood Vessels ◽  
Left Ventricular ◽  
Functional Changes ◽  
Healthy Humans ◽  
Vascular Ageing

There is a continuum of expression of cardiac structural and functional alterations that occurs with ageing in healthy humans, and these age-associated cardiac changes seem to be relevant to the increase in left ventricular hypertrophy, chronic heart failure, and arrhythmia that are commonly observed with increasing age. This chapter describes the structural and functional changes in the ageing process of the heart and blood vessels, and provides an overview of representative cardiovascular disease caused by ageing including hypertension, atherosclerosis, and heart failure. In addition, an outline of interventions that have be utilized to prevent and treat ageing related cardiovascular diseases is provided.

scholarly journals A patient with cardiovascular disease and anaemia: fatal combination or consistent pattern?

2020 ◽  
pp. 81-85
Author(s):  
N. O. Khovasova ◽  
A. V. Naumov
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Elderly Patient ◽  
Cardiovascular Diseases ◽  
Chronic Heart Failure ◽  
Clinical Case ◽  
Consistent Pattern ◽  
Normocytic Anemia ◽  
Somatic Diseases

Anemia is  a common clinical and laboratory syndrome, complicating many somatic diseases. Of particular importance is the reduction of hemoglobin in patients with cardiovascular diseases. Anemia increases both the frequency and prognosis of cardiovascular disease. The article presents a  typical clinical case of  an elderly patient with chronic heart failure and normocytic anemia, presents the algorithm of management and tactics of treatment of anemia.

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