To the Mechanism of Adrenaline Damage to the Heart Tissue and the Mechanism of Cardioprotection by Neonatal, Xenogenic, Cardiac Cells. Dynamics of Creatine Phosphate, Lactate and Malondialdehyde

Cardiac tissue engineering aims to generate in vivo-like functional tissue for the study of cardiac development, homeostasis, and regeneration. Since the heart is composed of various types of cells and extracellular matrix with a specific microenvironment, the fabrication of cardiac tissue in vitro requires integrating technologies of cardiac cells, biomaterials, fabrication, and computational modeling to model the complexity of heart tissue. Here, we review the recent progress of engineering techniques from simple to complex for fabricating matured cardiac tissue in vitro. Advancements in cardiomyocytes, extracellular matrix, geometry, and computational modeling will be discussed based on a technology perspective and their use for preparation of functional cardiac tissue. Since the heart is a very complex system at multiscale levels, an understanding of each technique and their interactions would be highly beneficial to the development of a fully functional heart in cardiac tissue engineering.

Download Full-text

Protective effect of creatine against inhibition by methylglyoxal of mitochondrial respiration of cardiac cells

Biochemical Journal ◽

10.1042/bj20021576 ◽

2003 ◽

Vol 372 (2) ◽

pp. 661-669 ◽

Cited By ~ 20

Author(s):

Soumya Sinha ROY ◽

Swati BISWAS ◽

Manju RAY ◽

Subhankar RAY

Keyword(s):

Creatine Kinase ◽

Protective Effect ◽

Mitochondrial Respiration ◽

Therapeutic Potential ◽

Ehrlich Ascites Carcinoma ◽

Creatine Phosphate ◽

Inhibitory Effect ◽

Cardiac Cells ◽

Protective Effects ◽

Tissue Slices

Previous publications from our laboratory have shown that methylglyoxal inhibits mitochondrial respiration of malignant and cardiac cells, but it has no effect on mitochondrial respiration of other normal cells [Biswas, Ray, Misra, Dutta and Ray (1997) Biochem. J. 323, 343–348; Ray, Biswas and Ray (1997) Mol. Cell. Biochem. 171, 95–103]. However, this inhibitory effect of methylglyoxal is not significant in cardiac tissue slices. Moreover, post-mitochondrial supernatant (PMS) of cardiac cells could almost completely protect the mitochondrial respiration against the inhibitory effect of methylglyoxal. A systematic search indicated that creatine present in cardiac cells is responsible for this protective effect. Glutathione has also some protective effect. However, creatine phosphate, creatinine, urea, glutathione disulphide and β-mercaptoethanol have no protective effect. The inhibitory and protective effects of methylglyoxal and creatine respectively on cardiac mitochondrial respiration were studied with various concentrations of both methylglyoxal and creatine. Interestingly, neither creatine nor glutathione have any protective effect on the inhibition by methylglyoxal on the mitochondrial respiration of Ehrlich ascites carcinoma cells. The creatine and glutathione contents of several PMS, which were tested for the possible protective effect, were measured. The activities of two important enzymes, namely glyoxalase I and creatine kinase, which act upon glutathione plus methylglyoxal and creatine respectively, were also measured in different PMS. Whether mitochondrial creatine kinase had any role in the protective effect of creatine had also been investigated using 1-fluoro-2,4-dinitrobenzene, an inhibitor of creatine kinase. The differential effect of creatine on mitochondria of cardiac and malignant cells has been discussed with reference to the therapeutic potential of methylglyoxal.

Download Full-text

Isolation and characterization of mitochondria and lysosome from isoproterenol induced cardiotoxic rats

South Asian Journal of Engineering and Technology ◽

10.26524/sajet190804 ◽

2019 ◽

Vol 8 (1) ◽

pp. 12-18

Author(s):

Malathi Mangalanathan ◽

Tamiloli Devendhiran ◽

Saraswathi Uthamaramasamy ◽

Keerthika Kumarasamy ◽

K Mohanraj ◽

...

Keyword(s):

Heart Tissue ◽

Cardiac Cells ◽

Marker Enzymes ◽

Membrane Function ◽

Biochemical Alterations ◽

Isolation And Characterization ◽

The Stability ◽

Membrane Pretreatment ◽

Hydroethanolic Extract

Mitochondrial and lysosomal membranes are prominent membranes of cardiac cells and are the factors that determine membrane function in myocardial ischemia. In this study, isolation of mitochondria and lysosome from heart tissue under the control, isoproterenol (ISO) (8.5mg/100g) induced cardiotoxic rats and oral pretreatment with Z. armatum fruit (200, 400mg/kg body weight) treated rats. Further characterization of marker enzymes was done. A decreased in the activity of all the mitochondrial and lysosomal marker enzymes in ISO administered cardiotoxic rats when compared to control rats which indicate ISO decreased the stability of the membrane. Pretreatment with hydroethanolic extract of Z. armatum fruit to ISO induced rats significantly reverted these biochemical alterations near to normal. The possible mechanism for the protection of heart mitochondria and lysosome against oxidative damage induced by ISO might be due to quenching of free radicals and enhancing the action of marker enzymes.

Download Full-text

Effect of Quercetin and Intermittent and Continuous Exercise on Catalase, Superoxide dismutase, and Malondialdehyde in the Heart of Rats with Colon Cancer

Basic & Clinical Cancer Research ◽

10.18502/bccr.v12i1.5733 ◽

2021 ◽

Author(s):

Behrooz Talaei ◽

Mohammad Panji ◽

Fatemeh Nazari Robati ◽

Sajjad Tezerji

Keyword(s):

Oxidative Stress ◽

Colorectal Cancer ◽

Superoxide Dismutase ◽

Cardiac Tissue ◽

Intermittent Exercise ◽

Heart Tissue ◽

Cardiac Cells ◽

Heart Cells ◽

Oxidative Stress Biomarkers ◽

Continuous Exercise

Background: Colorectal cancer is the fourth leading cause of death globally, and the second most common cancer in Europe. About 8% of all cancer-related deaths occur due to colorectal cancer, and the highest prevalence has been reported in Asia and Eastern Europe. Methods: In this experimental study, 80 rats were divided into two groups of cases (n=70) and controls (n=10). Colorectal cancer was induced weekly in rats by subcutaneous injection of 15 mg/kg Azoxymethane. The rats were then divided into 7 experimental subgroups of patients, saline, quercetin, intermittent exercise, continuous exercise, quercetin plus intermittent, and quercetin plus continuous exercise. Oxidative stress biomarkers, including superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) were measured in the rats’ heart tissue by the ELISA method. Data were analyzed using ANOVA by SPSS software. Results: Oxidative stress in heart cells increased due to colorectal cancer. Quercetin alone or in combination with exercise significantly increased mean levels of CAT and SOD in the heart tissue of rats compared with patient and saline groups (P<0.0001). In contrast, the MDA level was significantly decreased (P<0.05). Conclusion: Colorectal cancer increased the oxidative stress in cardiac cells. Quercetin alone improved oxidative stress in cardiac tissue, and its combination with exercise was more effective.

Download Full-text

Heart-on-a-Chip: An Investigation of the Influence of Static and Perfusion Conditions on Cardiac (H9C2) Cell Proliferation, Morphology, and Alignment

SLAS TECHNOLOGY Translating Life Sciences Innovation ◽

10.1177/2472630317705610 ◽

2017 ◽

Vol 22 (5) ◽

pp. 536-546 ◽

Cited By ~ 7

Author(s):

Anna Kobuszewska ◽

Ewelina Tomecka ◽

Kamil Zukowski ◽

Elzbieta Jastrzebska ◽

Michal Chudy ◽

...

Keyword(s):

Lab On A Chip ◽

Heart Tissue ◽

Cardiac Cells ◽

H9c2 Cell ◽

Cardiac Diseases ◽

H9c2 Cells ◽

Parallel Microchannels ◽

Static Conditions ◽

Longitudinal Channel ◽

Number Of Cells

Lab-on-a-chip systems are increasingly used as tools for cultures and investigation of cardiac cells. In this article, we present how the geometry of microsystems and microenvironmental conditions (static and perfusion) influence the proliferation, morphology, and alignment of cardiac cells (rat cardiomyoblasts—H9C2). Additionally, studies of cell growth after incubation with verapamil hydrochloride were performed. For this purpose, poly(dimethylsiloxane) (PDMS)/glass microfluidic systems with three different geometries of microchambers (a circular chamber, a longitudinal channel, and three parallel microchannels separated by two rows of micropillars) were prepared. It was found that static conditions did not enhance the growth of H9C2 cells in the microsystems. On the contrary, perfusion conditions had an influence on division, morphology, and the arrangement of the cells. The highest number of cells, their parallel orientation, and their elongated morphology were obtained in the longitudinal microchannel. It showed that this kind of microsystem can be used to understand processes in heart tissue in detail and to test newly developed compounds applied in the treatment of cardiac diseases.

Download Full-text

Phytosterol supplementation reduces metabolic activity and slows cell growth in cultured rat cardiomyocytes

British Journal Of Nutrition ◽

10.1017/s0007114511000626 ◽

2011 ◽

Vol 106 (4) ◽

pp. 540-548 ◽

Cited By ~ 14

Author(s):

Francesca Danesi ◽

Federico Ferioli ◽

Maria Fiorenza Caboni ◽

Elisa Boschetti ◽

Mattia Di Nunzio ◽

...

Keyword(s):

Cell Growth ◽

Metabolic Activity ◽

Membrane Integrity ◽

Cholesterol Content ◽

Heart Tissue ◽

Cardiac Cells ◽

Neonatal Rat ◽

Cholesterol Lowering ◽

Rat Cardiomyocytes ◽

Slowing Down

Besides being cholesterol-lowering agents, phytosterols (PS) can inhibit the growth and development of tumours. The anti-neoplastic activity is accounted for by PS incorporation into cell membranes, resulting in the interference of membrane functionality. The similarity between the PS cholesterol-lowering and anti-neoplastic effective doses deserves attention on the possible adverse effects even in non-neoplastic cells. To date, few studies have addressed the clarification of this important issue. In the present study, we supplemented primary, non-neoplastic neonatal rat cardiomyocytes with two different PS concentrations (3 or 6 μg/ml), both within the range of human plasma concentration. Cardiac cells were chosen as an experimental model since the heart has been reported as the target organ for subchronic toxicity of PS. Following supplementation, a dose-dependent incorporation of PS and a decrease in cholesterol content were clearly evidenced. PS did not induce apoptosis but caused a reduction in metabolic activity (measured as 3-(4,5-dimethyldiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) conversion) and a slowing down of cell growth. The lower MTT conversion and the similar lactate dehydrogenase release could suggest that PS more efficiently target mitochondria than plasma membrane integrity. The replacement of cholesterol by PS could also have caused the observed slowing down of cell growth and the reduction in metabolic activity, which could rely on the PS increase, cholesterol decrease, or both. The present study is the first report on the effect of PS in cardiac cells, and although it is difficult to translate the obtained results to the health of heart tissue, it raises concerns about the safety of long-term exposure to physiologically relevant PS concentrations.

Download Full-text

Energy dependence of enzyme release from hypoxic isolated perfused rat heart tissue

Journal of Applied Physiology ◽

10.1152/jappl.1988.65.4.1855 ◽

1988 ◽

Vol 65 (4) ◽

pp. 1855-1860 ◽

Cited By ~ 14

Author(s):

J. P. Kehrer ◽

Y. Park ◽

H. Sies

Keyword(s):

Lactate Dehydrogenase ◽

Rat Heart ◽

Creatine Phosphate ◽

Heart Tissue ◽

Enzyme Release ◽

Free Medium ◽

Perfusion Medium ◽

Perfused Rat Heart ◽

Rat Hearts ◽

Sudden Release

There is a sudden release of intracellular constituents upon reoxygenation of isolated perfused hypoxic heart tissue (O2 paradox) or on perfusion with calcium-free medium after a period of hypoxia. Rat hearts were perfused by the method of Langendorff (Pfluegers Arch. 61: 291-332, 1895) with Krebs-Henseleit medium containing 10 mM glucose. Hearts were equilibrated for 30 min, followed by 90 min of hypoxia or 60 min of hypoxia and 30 min of reoxygenation. The massive enzyme release observed upon reoxygenation after 60 min of hypoxia was prevented by infusing 0.5 or 5 mM cyanide 5 min before reoxygenation. Lactate dehydrogenase (LDH) release commenced immediately upon withdrawal of cyanide. Hearts perfused with calcium-free medium throughout hypoxia did not release increased amounts of LDH at reoxygenation. Perfusing heart tissue with medium containing 0 or 25 microM calcium, but not 0.25 or 2.5 mM, after 50 min of hypoxia initiated a release of cardiac LDH, which was not further enhanced by reoxygenation. Enzyme release was significantly inhibited when the calcium-free perfusion medium included 10 mM 2-deoxyglucose (replacing glucose), 0.5 mM dinitrophenol, or 2.5 mM cyanide. Histologically, hearts perfused with calcium-free medium after 50 min of hypoxia showed areas of severe necrosis and contracture without any evidence of the contraction bands that were seen in hearts reoxygenated in the presence of calcium. Cardiac ATP and creatine phosphate (PCr) levels were significantly decreased after 50-60 min of hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Download Full-text

Energy transport from mitochondria to myofibril by a creatine phosphate shuttle in cardiac cells

AJP Cell Physiology ◽

10.1152/ajpcell.1983.245.5.c423 ◽

1983 ◽

Vol 245 (5) ◽

pp. C423-C427 ◽

Cited By ~ 50

Author(s):

G. McClellan ◽

A. Weisberg ◽

S. Winegrad

Keyword(s):

Small Molecules ◽

Inorganic Phosphate ◽

Energy Transport ◽

Adenine Nucleotide ◽

Surface Membrane ◽

Creatine Phosphate ◽

Cardiac Cells ◽

Bathing Solution ◽

Resting Tension ◽

Creatine Phosphate Shuttle

In hyperpermeable cardiac cells, in which the surface membrane has been made highly permeable to small molecules and ions, resting tension increases when the concentration of ATP falls below 200 microM. Peak resting tension occurs in 10 microM ATP and equals 60% of maximum Ca-activated force in 5 mM ATP. The mitochondria in hyperpermeable cells can maintain an ATP concentration above 200 microM if supplied with O2, substrate, ADP, and inorganic phosphate (Pi). Removal of ATP from the bathing solution does not increase resting tension as long as creatine phosphate is present. However O2, substrate, and Pi cannot lower resting tension in the absence of ATP and creatine phosphate. These results are interpreted as evidence for adenine nucleotide tightly bound to the myofibrils and a creatine phosphate shunt of energy from the mitochondria to the myofibrils.

Download Full-text

On the benefit of magnetic magnesium nanocarrier in cardiovascular toxicity of aluminum phosphide

Toxicology and Industrial Health ◽

10.1177/0748233711425074 ◽

2011 ◽

Vol 29 (2) ◽

pp. 126-135 ◽

Cited By ~ 18

Author(s):

Maryam Baeeri ◽

Marjan Shariatpanahi ◽

Amir Baghaei ◽

Seyedeh Farnaz Ghasemi-Niri ◽

Hamidreza Mohammadi ◽

...

Keyword(s):

Lipid Peroxidation ◽

Considerable Increase ◽

Lethal Dose ◽

Heart Tissue ◽

Cardiac Cells ◽

Intragastric Administration ◽

Aluminum Phosphide ◽

Antioxidant Power ◽

Effective Combination ◽

Study Support

The present study was designed to determine the effect of a new 25Mg2+-carrying nanoparticle (25MgPMC16) on energy depletion, oxidative stress, and electrocardiographic (ECG) parameters on heart tissue of the rats poisoned by aluminum phosphide (AlP). 25MgPMC16 at doses of 0.025, 0.05, and 0.1 median lethal dose (LD50 = 896 mg/kg) was administered intravenously (iv) 30 min after a single intragastric administration of AlP (0.25 LD50). Sodium bicarbonate (Bicarb; 2 mEq/kg, iv) was used as the standard therapy. After anesthesia, the animals were rapidly connected to an electronic cardiovascular monitoring device for monitoring of ECG, blood pressure (BP), and heart rate (HR). Later lipid peroxidation, antioxidant power, ATP/ADP ratio, and Mg concentration in the heart were evaluated. Results indicated that after AlP administration, BP and HR decreased while R-R duration increased. 25MgPMC16 significantly increased the BP and HR at all doses used. We found a considerable increase in antioxidant power, Mg level in the plasma and the heart and a reduction in lipid peroxidation and ADP/ATP ratio at various doses of 25MgPMC16, but 25MgPMC16-0.025 + Bicarb was the most effective combination therapy. The results of this study support that 25MgPMC16 can increase heart energy by active transport of Mg inside the cardiac cells.25MgPMC16 seems ameliorating AlP-induced toxicity and cardiac failure necessitating further studies.

Download Full-text

Transit and integration of extracellular mitochondria in human heart cells

10.1101/157164 ◽

2017 ◽

Author(s):

Douglas B. Cowan ◽

Rouan Yao ◽

Jerusha K. Thedsanamoorthy ◽

David Zurakowski ◽

Pedro J. del Nido ◽

...

Keyword(s):

Contractile Function ◽

Cardiac Fibroblasts ◽

Three Dimensional ◽

Heart Tissue ◽

Cardiac Cells ◽

Heart Cells ◽

Tissue Ischemia ◽

Isolated Mitochondria ◽

Wide Range ◽

The Impact

Tissue ischemia adversely affects the function of mitochondria, which results in impairment of oxidative phosphorylation and compromised recovery of the affected organ. The impact of ischemia on mitochondrial function has been most extensively studied in the heart because of the morbidity and mortality associated with injury to this organ. Because conventional methods to preserve cell viability and function following an ischemic injury are limited in their efficacy, we developed a unique approach to protect the heart by transplanting respiration-competent mitochondria isolated from a non-ischemic tissue to the ischemic region. Our experiments in animals have shown that transplantation of isolated mitochondria to injured heart tissue leads to decreases in cell death, increases in energy production, and improvements in contractile function. We also discovered that exogenously-derived mitochondria injected or perfused into ischemic hearts were readily internalized by cardiac cells through actin-dependent endocytosis. Here, we describe the use of three-dimensional super-resolution microscopy and transmission electron microscopy to determine the intracellular fate of exogenous mitochondria in non-dividing human iPS-derived cardiomyocytes and dividing primary human cardiac fibroblasts. We show isolated mitochondria are internalised in human cardiac cells within minutes and then transported to endosomes and lysosomes. The majority of exogenous mitochondria escape from these compartments and fuse with the endogenous mitochondrial network, while some organelles are degraded through hydrolysis. Understanding this process may guide the development of treatments directed at replacing or augmenting impaired mitochondria in ischemic tissues and provide new options to rejuvenate dysfunctional mitochondria in a wide range of human diseases and disorders.

Download Full-text