1,721,002 research outputs found
Novel aspects of excitation-contraction coupling in heart failure
No full textExcitation-contraction coupling is the process by which electrical activation is translated into contraction of a cardiac myocyte and thus the heart. In heart failure, expression, phosphorylation, and function of several intracellular proteins that are involved in excitation-contraction coupling are altered. The present review article summarizes central principles and highlights novel aspects of alterations in heart failure, focusing especially on recent findings regarding altered sarcoplasmic reticulum Ca2+-leak and late Na+-current without being able to cover all changes in full detail. These two pathomechanisms seem to play interesting roles with respect to systolic and diastolic dysfunction and may also be important for cardiac arrhythmias. Furthermore, the article outlines the translation of these novel findings into potential therapeutic approaches
Effects on recovery during, acidosis in cardiac myocytes overexpressing CaMKII
No full textRecovery of intracellular Ca transients and fractional shortening during late phase acidosis are suggested to be associated with CaMKII-dependent processes of which phospholamban (PLB) phosphorylation may play an important role. To test whether increased expression levels of CaMKII may further enhance recovery, we investigated myocytes from CaMKII delta(C) transgenic (TG) mice (cytosolic localized CaMKII) having heart failure vs. wildtype littermates (WT). Furthermore, mouse and rabbit myocytes overexpressing CaMI:I delta(C) using adenovirus-mediated gene transfer (vs. LacZ control) were investigated. Fractional shortening (% vs. resting cell length, % RCL was assessed during control conditions (pH 7.4) and during acidosis (pH 6.5). Ca transients were measured using fluo-3 (Delta F/F-0, 10 mu M). In WT mouse myocytes, fractional shortening clearly recovered by 90% from 4.6 +/- 0.6 to 7.2 +/- 0.7% RCL during late acidosis. In parallel, Ca transients increased from 2.01 +/- 0. 11 to 2.33:L 0. 15 Delta F/F-0. When blocking CaMKII (KN-93, I mu M), recovery of Ca transients and shortening could be completely abolished, In contrast, in CaMKII delta(C) TG mouse myocytes shortening recovered only by 32% from 3.4 +/- 0.6 to 4.4 +/- 0.5% RCL (P< 0.05 vs. WT using ANOVA). In parallel, Ca transients increased only slightly from 1.75 +/- 0.15 to 1.84 +/- 0.13 Delta F/F-0 (P< 0.05 vs. WT using ANOVA). In accordance, SR Ca content (measured by caffeine contractures, 10 mM) in WT significantly increased during late acidosis but not in CaMKII delta(C) TG mice. In contrast, in mouse and rabbit myocytes overexpressing CaMKII delta(C) by means of adenovirus-mediated gene transfer, recovery of fractional shortening and Ca transients was not impaired during late acidosis but even slightly improved vs. LacZ control (P<0.05 vs. CaMKII delta(C) using ANOVA for mouse and rabbit myocytes). This was associated with significantly increased SR Ca content during late acidosis in CaMKII delta(C) as compared to LacZ. CaMKII-dependent PLB Thr- 17 phosphorylation, contributing to increased SR Ca uptake, was significantly increased in CaMKII delta(C) transfected rabbit myocytes vs. LacZ in the light of unchanged SR Ca ATPase and PLB protein expression. CaMKII inhibition completely prevented recovery of all parameters in both CaMKII delta(C) and LacZ. In summary and in contrast to our initial hypothesis, we showed for the first time that TG CaMKII delta(C) overexpression (i.e., chronic overexpression) in mice with heart failure clearly resulted in impaired recovery associated with impaired SR Ca loading during late acidosis vs. WT. This may be due to decreased SR Ca ATPase and PLB expression as reported previously. In contrast, adenovirus-mediated gene transfer of CaMKII delta(C) in mouse and rabbit myocytes (i.e., acute overexpression) did not result in impaired but even slightly improved recovery associated with increased SR Ca load during late acidosis as compared to LacZ. This most likely was due to higher PLB Thr- 17 phosphorylation in CaMKII delta(C) myocytes. In conclusion, possible beneficial effects by therapeutical CaMKII delta(C) stimulation on the ability to recover from acidosis may be challenged by altered expression levels of its target proteins and should be carefully considered. (c) 2007 Elsevier Inc. All rights reserved
The Ca-calmodulin dependent kinase II: A promising target for future antiarrhythmic therapies?
No full textAbstractTreating arrhythmias is a challenge for clinicians because pharmacological therapies are often ineffective or have severe side effects. Patients with heart failure frequently present with supreventricular and ventricular arrhythmias. New antiarrhythmic therapies are needed that modulate the specific pathomechanisms underlying the development of cardiac arrhythmias and may have a better safety-profile. The Ca-calmodulin dependent kinase II (CaMKII) seems to be involved in the development of heart failure and arrhythmias and may therefore be a promising target for the development of antiarrhythmic therapies. The current review aims at discussing some novel as well as known cytosolic and sarcolemmal mechanisms involved in CaMKII-dependent arrhythmias without being able to cover all aspects known in the field. This article is part of a Special Issue entitled "Calcium Signaling in Heart"
Increased Diastolic Calcium Levels Due to CaMKII-Dependent Sarcoplasmic Reticulum Calcium Leak in Patients With Atrial Fibrillation
No full textEXPRESSION OF LYSYL OXIDASE-LIKE 2 (LOXL2) CORRELATES WITH LEFT ATRIAL SIZE AND FIBROTIC GENE EXPRESSION IN HUMAN ATRIAL FIBRILLATION
No full textbeta-adrenergic stimulation of Ca/calmodulin-dependent protein kinase II (CaMKII) overexpressing myocytes increases sarcoplasmic reticulum (SR) calcium leak causing KN-93 sensitive arrhythmias
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Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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