scholarly journals Morphology and Contractility of Cardiac Myocytes in Early Stages of Streptozotocin-Induced Diabetes Mellitus in Rats

2013 ◽  
pp. 489-501 ◽  
Author(s):  
M. CAGALINEC ◽  
I. WACZULÍKOVÁ ◽  
O. ULIČNÁ ◽  
D. CHORVAT
Keyword(s):  
Ventricular Myocytes ◽  
Calcium Transient ◽  
Detection Algorithm ◽  
Heart Tissue ◽  
Left Ventricular ◽  
Contour Detection ◽  
Point Of View ◽  
Calcium Handling ◽  
Early Stages ◽  
Streptozotocin Induced Diabetes

Diabetic cardiomyopathy is the leading cause of mortality in type 1 diabetes. Thus study of cardiomyocyte morphology and function during early stages of diabetes using modern analytical methods is of critical importance. Therefore, using confocal microscopy, we determined metric parameters, volumes and contractility, with calcium transients in isolated left-ventricular myocytes at one week after induction of diabetes in rats. Myocyte volume analysis from 3D confocal scans was performed using an automated contour detection algorithm that took the actual shape of the myocytes into account. We showed a significant reduction in myocyte volume in diabetic animals. We also showed a significant reduction in length and width but not in thickness of the myocytes, which suggests disproportional reorganization of the structure of the heart tissue during short-term diabetes. From a functional point of view, we observed a significant decrease in cell shortening at a stimulation frequency of 0.5 Hz. This was accompanied by a decrease in calcium transient amplitude. Together, these data suggest that impaired calcium handling is one of the factors that contributes to the observed decrease in myocyte shortening during early stages of streptozotocin-induced diabetes in rats.

scholarly journals Calcium handling in zebrafish ventricular myocytes

2011 ◽  
Vol 300 (1) ◽  
pp. R56-R66 ◽  
Author(s):  
Ping-Cheng Zhang ◽  
Anna Llach ◽  
Xiao Ye Sheng ◽  
Leif Hove-Madsen ◽  
Glen F. Tibbits
Keyword(s):  
Ventricular Myocytes ◽  
Cardiac Development ◽  
Calcium Transient ◽  
Membrane Potentials ◽  
Calcium Handling ◽  
Patch Clamp Technique ◽  
Cell Shortening ◽  
Calcium Dependent ◽  
Reverse Mode ◽  
Zebrafish Heart

The zebrafish is an important model for the study of vertebrate cardiac development with a rich array of genetic mutations and biological reagents for functional interrogation. The similarity of the zebrafish ( Danio rerio) cardiac action potential with that of humans further enhances the relevance of this model. In spite of this, little is known about excitation-contraction coupling in the zebrafish heart. To address this issue, adult zebrafish cardiomyocytes were isolated by enzymatic perfusion of the cannulated ventricle and were subjected to amphotericin-perforated patch-clamp technique, confocal calcium imaging, and/or measurements of cell shortening. Simultaneous recordings of the voltage dependence of the L-type calcium current ( ICa,L) amplitude and cell shortening showed a typical bell-shaped current-voltage ( I-V) relationship for ICa,L with a maximum at +10 mV, whereas calcium transients and cell shortening showed a monophasic increase with membrane depolarization that reached a plateau at membrane potentials above +20 mV. Values of ICa,L were 53, 100, and 17% of maximum at −20, +10, and +40 mV, while the corresponding calcium transient amplitudes were 64, 92, and 98% and cell shortening values were 62, 95, and 96% of maximum, respectively, suggesting that ICa,L is the major contributor to the activation of contraction at voltages below +10 mV, whereas the contribution of reverse-mode Na/Ca exchange becomes increasingly more important at membrane potentials above +10 mV. Comparison of the recovery of ICa,L from acute and steady-state inactivation showed that reduction of ICa,L upon elevation of the stimulation frequency is primarily due to calcium-dependent ICa,L inactivation. In conclusion, we demonstrate that a large yield of healthy atrial and ventricular myocytes can be obtained by enzymatic perfusion of the cannulated zebrafish heart. Moreover, zebrafish ventricular myocytes differed from that of large mammals by having larger ICa,L density and a monophasically increasing contraction-voltage relationship, suggesting that caution should be taken upon extrapolation of the functional impact of mutations on calcium handling and contraction in zebrafish cardiomyocytes.

Acute Administration of Chitosan Nanoparticles Increases Ca2+ Leak in Rat Cardiomyocytes

2014 ◽  
Vol 28 ◽  
pp. 29-38 ◽  
Author(s):  
Gayathri Narasimhan ◽  
David Ramiro de Alba-Aguayo ◽  
Ricardo Mondragón-Flores ◽  
Sirenia González-Pozos ◽  
Miyamin J. Miranda-Saturnino ◽  
...  
Keyword(s):  
Ventricular Myocytes ◽  
Polymeric Nanoparticles ◽  
Chitosan Nanoparticles ◽  
Left Ventricular ◽  
Calcium Handling ◽  
Acute Administration ◽  
Acute Effects ◽  
Rat Cardiomyocytes ◽  
Lack Of Information ◽  
Rising Time

Polymeric nanoparticles like chitosan nanoparticles may be used to deliver drugs to particular organs, such as heart. However, due to the lack of information about acute effects of chitosan nanoparticles in cardiac calcium handling, we evaluated the same in intact rat left ventricular myocytes. Chitosan nanoparticles were synthesized by ionic gelation method for three different concentrations of chitosan and tripolyphosphate (TPP) such as 1:1, 2:1 and 3:1, respectively. The size of the particles was below 100 nm for the 2:1 and 3:1 chitosan:TPP ratio and 300 nm for 1:1 ratio. The particles synthesized in 3:1 ratio were incubated for 0, 15, 30 and 60 minutes with Fluo-3 loaded cardiomyocytes, their effects were evaluated in local Ca2+ release events using confocal microscopy and compared with control cells. Chitosan nanoparticles increased the amplitude and size of Ca2+ spark by 14.1% and 24.1% at 30 minutes of incubation; while the increment was 24.7% and 28.4% at 60 minutes respectively. Accordingly, rising time of Ca2+ sparks was decreased by 47% at 30 minutes. These changes were reflected in increased local Ca2+ flux by 58.3% and spark-mediated Ca2+ leak by 145.9% and 146.5% at 30, and 60 minutes, respectively. Hence, these results indicate that chitosan nanoparticles modify the properties of local Ca2+ release events mainly at short incubation times and must be taken into account while using these nanoparticles in drug delivery.

scholarly journals Role of Adipose-Derived Mesenchymal Stem Cells in the Regeneration of Cardiac Tissue and Improvement of Cardiac Function: a Narrative Review

2020 ◽  
Vol 11 (1) ◽  
pp. 8446-8456
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cardiac Function ◽  
Cardiac Fibrosis ◽  
Cardiac Tissue ◽  
Trichostatin A ◽  
Heart Tissue ◽  
Left Ventricular ◽  
Point Of View

Recent efforts have made in order to novel therapeutic approaches to reduce the heavy cardiovascular burden. The use of cell therapy and applying stem cell-based therapies has received much attention; of particular interest are adipose-derived mesenchymal stem cells (ADSCs). The present review aimed to review the studies which examined and researched various aspects of ADSCs to improve cardiac function. A comprehensive review of all articles assessed and discussed the application of ADSCs in the improvement of cardiac tissue renewing and cardiomyocytes regeneration was planned and conducted by the two reviewers. The initial literature search revealed a total of 153 articles that, of those, 34 were considered eligible. From the perspective of heart tissue regeneration, the inductive role of ADSCs in sensing mechanical stimulation and produce collagen and elastin scaffolds, vascularizing cardiac tissue, and exosomes (vesicles derived from ADSCs) in ADSCs‐mediated myocardial protection has indicated. In the process of ADSCs differentiation to cardiomyocyte- like cells, the role of various targeted pathways have been identified that can be influenced by different elements such as TGF-beta1, phorbol myristate acetate, Angiotensin II, Rho-associated kinases, 5-Azaytidine, Sodium valproate, fibrin scaffold and trichostatin A have been highlighted. In the final, from a therapeutic point of view, the effectiveness of ADMSCs differentiation to cardiomyocytes as improving left ventricular functional state has been discussed. Summarizing the studies confirms a significant improvement in cardiac function following direct application of ADSCs or their transformation to cardiomyocytes by stimulating or inhibiting various cellular pathways leading reducing oxidative stress and inflammatory bed, reducing cardiomyocyte apoptosis, attenuating cardiac fibrosis, reducing the infiltration of immune cells and collagen deposition, and enhancing angiogenesis.

Abstract 154: Hydrogen Peroxide-Induced Contractile Dysfunction is Mediated Through Oxidation of SERCA on Cysteine-674

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Steve Lancel ◽  
Jingmei Zhang ◽  
Gabriela M Kuster ◽  
Jia Ying ◽  
David R Pimentel ◽  
...  
Keyword(s):  
Ventricular Myocytes ◽  
Calcium Transient ◽  
Calcium Handling ◽  
Contractile Dysfunction ◽  
Post Translational Modification ◽  
Post Translational Modifications ◽  
Adenoviral Infection ◽  
Cell Shortening ◽  
Endoplasmic Reticulum Calcium ◽  
Adult Rat

Background: Reactive oxygen species (ROS) are critical mediators of cardiomyocyte contractile dysfunction. We previously reported that H 2 O 2 induces thiol oxidative post-translational modifications of the calcium handling protein sarco/endoplasmic reticulum calcium ATPase (SERCA), leading to a reduction of its activity and contractile dysfunction. Here, we tested the hypothesis that cysteine-674 of SERCA is critical for H 2 O 2 -induced contractile dysfunction in adult rat ventricular myocytes (ARVM). Methods: Overexpression of wild-type (WT) or mutant SERCA, in which cysteine-674 was mutated to serine (C674S), was accomplished by 36 hours of adenoviral infection. ARVM were paced at 5Hz and superfused with 100μM H 2 O 2 . Cell shortening and calcium transients were measured over 20 minutes using video-edge detection and fura-2 fluorescence. Thiol oxidation of SERCA was assessed using biotinylated iodoacet- amide (BIAM)-labeling. Results: After 14min of H 2 O 2 exposure, cell shortening was markedly reduced in WT-SERCA overexpressing ARVM (−43 ± 21%) but not in C674S-SERCA overex-pressing ARVM (−49% ± 31%, p<0.05 vs WT-SERCA, n=21–24/group). Time of 50% cell relengthening was prolonged by 15 ± 5% in WT-SERCA ARVM (p<0.05 vs time 0) but not in C674S-SERCA cells (+1 ± 4%, NS vs time 0). Compared with WT-SERCA ARVM, expression of C674S-SERCA attenuated the H 2 O 2 -induced reduction in calcium transient amplitude (−51 ± 11% vs −87 ± 6%, p<0.05 C674S-SERCA vs WT-SERCA). The 50% calcium reuptake time was prolonged in WT-SERCA compared with C674S-SERCA ARVM (60 ± 3ms vs 46 ± 3ms, p<0.05), reflecting a decrease in SERCA activity in WT-SERCA but not in C674S-SERCA ARVM. H 2 O 2 decreased BIAM-labeling in ARVM overexpressing WT-SERCA by 40% ± 7% (p<0.01,n=3) but failed to decrease BIAM-labeling in ARVM overexpressing C674S-SERCA. Conclusion: Increased thiol oxidative post-translational modification was correlated with a reduced SERCA activity and calcium handling abnormalities, and these effects were attenuated in ARVM overexpressing mutated SERCA modified at Cys674. These findings suggest that oxidation on Cys674 of SERCA is responsible for H 2 O 2 -induced reduction in its activity leading to contractile dysfunction.

scholarly journals Comparison of contraction and calcium handling between right and left ventricular myocytes from adult mouse heart: a role for repolarization waveform

2006 ◽  
Vol 571 (1) ◽  
pp. 131-146 ◽  
Author(s):  
Richard P. Kondo ◽  
Dorothy A. Dederko ◽  
Christine Teutsch ◽  
Jacqueline Chrast ◽  
Daniele Catalucci ◽  
...  
Keyword(s):  
Adult Mouse ◽  
Ventricular Myocytes ◽  
Left Ventricular ◽  
Calcium Handling ◽  
Mouse Heart

Cardiac mitofusin-1 is declined in non-responding patients with idiopathic dilated cardiomyopathy

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
Y Hsiao ◽  
I Shimizu ◽  
T Wakasugi ◽  
S Jiao ◽  
T Watanabe ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Heart Failure ◽  
Ventricular Myocytes ◽  
Severe Heart Failure ◽  
Left Ventricular ◽  
Neonatal Rat ◽  
Heart Failure Patients ◽  
Underlying Mechanisms ◽  
Neonatal Rat Ventricular Myocytes ◽  
Mitofusin 1

Abstract Background/Introduction Mitochondria are dynamic regulators of cellular metabolism and homeostasis. The dysfunction of mitochondria has long been considered a major contributor to aging and age-related diseases. The prognosis of severe heart failure is still unacceptably poor and it is urgent to establish new therapies for this critical condition. Some patients with heart failure do not respond to established multidisciplinary treatment and they are classified as “non-responders”. The outcome is especially poor for non-responders, and underlying mechanisms are largely unknown. Purpose Studies indicate mitochondrial dysfunction has causal roles for metabolic remodeling in the failing heart, but underlying mechanisms remain to be explored. This study tried to elucidate the role of Mitofusin-1 in a failing heart. Methods We examined twenty-two heart failure patients who underwent endomyocardial biopsy of intraventricular septum. Patients were classified as non-responders when their left-ventricular (LV) ejection fraction did not show more than 10% improvement at remote phase after biopsy. Fourteen patients were classified as responders, and eight as non-responders. Electron microscopy, quantitative PCR, and immunofluorescence studies were performed to explore the biological processes or molecules involved in failure to respond. In addition to studies with cardiac tissue specific knockout mice, we also conducted functional in-vitro studies with neonatal rat ventricular myocytes. Results Twenty-two patients with IDCM who underwent endomyocardial biopsy were enrolled in this study, including 14 responders and 8 non-responders. Transmission electron microscopy (EM) showed a significant reduction in mitochondrial size in cardiomyocytes of non-responders compared to responders. Quantitative PCR revealed that transcript of mitochondrial fusion protein, Mitofusin-1, was significantly reduced in non-responders. Studies with neonatal rat ventricular myocytes (NRVMs) indicated that the beta-1 adrenergic receptor-mediated signaling pathway negatively regulates Mitofusin-1 expression. Suppression of Mitofusin-1 resulted in a significant reduction in mitochondrial respiration of NRVMs. We generated left ventricular pressure overload model with thoracic aortic constriction (TAC) in cardiac specific Mitofusin-1 knockout model (c-Mfn1 KO). Systolic function was reduced in c-Mfn1 KO mice, and EM study showed an increase in dysfunctional mitochondria in the KO group subjected to TAC. Conclusions Mitofusin-1 becomes a biomarker for non-responders with heart failure. In addition, our results suggest that therapies targeting mitochondrial dynamics and homeostasis would become next generation therapy for severe heart failure patients. Funding Acknowledgement Type of funding source: None

scholarly journals Percolation and tortuosity in heart-like cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
R. Rabinovitch ◽  
Y. Biton ◽  
D. Braunstein ◽  
I. Aviram ◽  
R. Thieberger ◽  
...  
Keyword(s):  
Action Potential ◽  
Forest Fire ◽  
Sinus Node ◽  
Heart Tissue ◽  
Point Of View ◽  
Physical Point ◽  
Electrical Currents ◽  
Single Wave ◽  
Heart Arrhythmia ◽  
The One

AbstractIn the last several years, quite a few papers on the joint question of transport, tortuosity and percolation have appeared in the literature, dealing with passage of miscellaneous liquids or electrical currents in different media. However, these methods have not been applied to the passage of action potential in heart fibrosis (HF), which is crucial for problems of heart arrhythmia, especially of atrial tachycardia and fibrillation. In this work we address the HF problem from these aspects. A cellular automaton model is used to analyze percolation and transport of a distributed-fibrosis inflicted heart-like tissue. Although based on a rather simple mathematical model, it leads to several important outcomes: (1) It is shown that, for a single wave front (as the one emanated by the heart's sinus node), the percolation of heart-like matrices is exactly similar to the forest fire case. (2) It is shown that, on the average, the shape of the transport (a question not dealt with in relation to forest fire, and deals with the delay of action potential when passing a fibrotic tissue) behaves like a Gaussian. (3) Moreover, it is shown that close to the percolation threshold the parameters of this Gaussian behave in a critical way. From the physical point of view, these three results are an important contribution to the general percolation investigation. The relevance of our results to cardiological issues, specifically to the question of reentry initiation, are discussed and it is shown that: (A) Without an ectopic source and under a mere sinus node operation, no arrhythmia is generated, and (B) A sufficiently high refractory period could prevent some reentry mechanisms, even in partially fibrotic heart tissue.

scholarly journals Effects of acidosis on resting cytosolic and mitochondrial Ca2+ in mammalian myocardium.

1993 ◽  
Vol 102 (3) ◽  
pp. 575-597 ◽  
Author(s):  
G Gambassi ◽  
R G Hansford ◽  
S J Sollott ◽  
B A Hogue ◽  
E G Lakatta ◽  
...  
Keyword(s):  
Lactic Acid ◽  
Ventricular Myocytes ◽  
Free Acid ◽  
Left Ventricular ◽  
Ruthenium Red ◽  
Acetoxymethyl Ester ◽  
Cytosolic Ph ◽  
Bicarbonate Buffer ◽  
Adult Rat ◽  
Mammalian Myocardium

Acidosis increases resting cytosolic [Ca2+], (Cai) of myocardial preparations; however, neither the Ca2+ sources for the increase in Cai nor the effect of acidosis on mitochondrial free [Ca2+], (Cam) have been characterized. In this study cytosolic pH (pHi) was monitored in adult rat left ventricular myocytes loaded with the acetoxymethyl ester (AM form) of SNARF-1. A stable decrease in the pHi of 0.52 +/- 0.05 U (n = 16) was obtained by switching from a bicarbonate buffer equilibrated with 5% CO2 to a buffer equilibrated with 20% CO2. Electrical stimulation at either 0.5 or 1.5 Hz had no effect on pHi in 5% CO2, nor did it affect the magnitude of pHi decrease in response to hypercarbic acidosis. Cai was measured in myocytes loaded with indo-1/free acid and Cam was monitored in cells loaded with indo-1/AM after quenching cytosolic indo-1 fluorescence with MnCl2. In quiescent intact myocytes bathed in 1.5 mM [Ca2+], hypercarbia increased Cai from 130 +/- 5 to 221 +/- 13 nM. However, when acidosis was effected in electrically stimulated myocytes, diastolic Cai increased more than resting Cai in quiescent myocytes, and during pacing at 1.5 Hz diastolic Cai was higher (285 +/- 17 nM) than at 0.5 Hz (245 +/- 18 nM; P &lt; 0.05). The magnitude of Cai increase in quiescent myocytes was not affected either by sarcoplasmic reticulum (SR) Ca2+ depletion with ryanodine or by SR Ca2+ depletion and concomitant superfusion with a Ca(2+)-free buffer. In unstimulated intact myocytes hypercarbia increased Cam from 95 +/- 12 to 147 +/- 19 nM and this response was not modified either by ryanodine and a Ca(2+)-free buffer or by 50 microM ruthenium red in order to block the mitochondrial uniporter. In mitochondrial suspensions loaded either with BCECF/AM or indo-1/AM, acidosis produced by lactic acid addition decreased both intra- and extramitochondrial pH and increased Cam. Studies of mitochondrial suspensions bathed in indo-1/free acid-containing solution showed an increase in extramitochondrial Ca2+ after the addition of lactic acid. Thus, in quiescent myocytes, cytoplasmic and intramitochondrial buffers, rather than transsarcolemmal Ca2+ influx or SR Ca2+ release, are the likely Ca2+ sources for the increase in Cai and Cam, respectively; additionally, Ca2+ efflux from the mitochondria may contribute to the raise in Cai. In contrast, in response to acidosis, diastolic Cai in electrically stimulated myocytes increases more than resting Cai in quiescent cells; this suggests that during pacing, net cell Ca2+ gain contributes to enhance diastolic Cai.

scholarly journals Transcriptomic analysis of the cardiac left ventricle in a rodent model of diabetic cardiomyopathy: molecular snapshot of a severe myocardial disease

2007 ◽  
Vol 28 (3) ◽  
pp. 284-293 ◽  
Author(s):  
Sarah Glyn-Jones ◽  
Sarah Song ◽  
Michael A. Black ◽  
Anthony R. J. Phillips ◽  
Soon Y. Choong ◽  
...  
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Molecular Basis ◽  
Cardiovascular Complications ◽  
Left Ventricular ◽  
Myocardial Disease ◽  
Chronic Hyperglycemia ◽  
Expression Of Genes ◽  
Streptozotocin Induced Diabetes ◽  
Quantitative Verification ◽  
Disproportionate Number

Heart disease is the major cause of death in diabetes, a disorder characterized by chronic hyperglycemia and cardiovascular complications. Diabetic cardiomyopathy (DCM) is increasingly recognized as a major contributor to diastolic dysfunction and heart failure in diabetes, but its molecular basis has remained obscure, in part because of its multifactorial origins. Here we employed comparative transcriptomic methods with quantitative verification of selected transcripts by reverse transcriptase quantitative PCR to characterize the molecular basis of DCM in rats with streptozotocin-induced diabetes of 16-wk duration. Diabetes caused left ventricular disease that was accompanied by significant changes in the expression of 1,614 genes, 749 of which had functions assignable by Gene Ontology classification. Genes corresponding to proteins expressed in mitochondria accounted for a disproportionate number of those whose expression was significantly modified in DCM, consistent with the idea that the mitochondrion is a key target of the pathogenic processes that cause myocardial disease in diabetes. Diabetes also induced global perturbations in the expression of genes regulating cardiac fatty acid metabolism, whose dysfunction is likely to play a key role in the promotion of oxidative stress, thereby contributing to the pathogenesis of diabetic myocardial disease. In particular, these data point to impaired regulation of mitochondrial β-oxidation as central in the mechanisms that generate DCM pathogenesis. This study provides a comprehensive molecular snapshot of the processes leading to myocardial disease in diabetes.

Sign in / Sign up

Export Citation Format

Share Document