Cyclosporine-Induced Apoptosis in Human Cardiomyocytes Through P53-Dependent Pathway

2000 ◽  
Vol 6 (S2) ◽  
pp. 632-633
Author(s):  
M. Kinjo ◽  
C. Wei
Keyword(s):  
Heart Surgery ◽  
Cardiac Tissue ◽  
Open Heart Surgery ◽  
Related Gene ◽  
P53 Expression ◽  
Human Cardiomyocytes ◽  
Significant Toxicity ◽  
Induced Apoptosis ◽  
Dependent Pathway ◽  
Apoptosis Related Gene

Cyclosporine A (CsA) is the most effective and widely used immunosuppressant drug in heart, lung and kidney transplantation. However, the effect of CsA is limited by the significant toxicity. The mechanism of CsA-induced toxicity is remaining controversial. Cellular apoptosis is being suggested as a possible mediator of CsA toxicity. To date, regarding the effects of CsA on apoptosis and apoptosis-related gene regulation in cardiomyocytes remain unclear. Therefore, the current study was designed to investigate the effect of CsA on apoptosis and apoptosis-related gene p53 expression in human cardiomyocytes. We hypothesized that CsA induces apoptosis in human cardiomyocytes through p53-dependent pathway.Human cardiac atrial tissue was obtained from open-heart surgery (n=5). The cardiac tissue was minced and incubated in the special tissue culture system for 24 hours in the absence or presence of CsA (10-7 M). To detect the DNA fragmentation, in situ terminal deoxymucleotidyl transferase dUTP nick end labeling (TUNEL) was performed.

The Action of C-Type Natriuretic Peptide on Apoptosis and P53 Expression in Human Cardiomyocytes

2000 ◽  
Vol 6 (S2) ◽  
pp. 622-623
Author(s):  
K. Seta ◽  
Y. Matsuda ◽  
C. Wei
Keyword(s):  
Natriuretic Peptide ◽  
Heart Surgery ◽  
Cardiac Tissue ◽  
Open Heart Surgery ◽  
Severe Congestive Heart Failure ◽  
P53 Expression ◽  
Human Cardiomyocytes ◽  
Human Cardiac Tissue ◽  
Apoptosis Related Gene

C-type natriuretic peptide (CNP) is endothelial cell origin and has potent vasodilatory and antimitogenic actions. We reported that CNP was markedly increased in human cardiac tissue with severe congestive heart failure. To date, the effects of CNP on cardiomyocyte growth and death remain unclear. Therefore, the present study was designed to investigate the actions of CNP on apoptosis and apoptosis-related gene p53 expression in human cardiomyocytes.Human cardiac atrial tissue was obtained from open-heart surgery (n=6). The cardiac tissue was minced and incubated in the special tissue culture system in the absence or presence of CNP (10-7 M) for 24 hours. These studies were repeated with HS-142-1 (HS, 10-6 M), a natriuretic peptide biological receptor antagonist. To detect the DNA fragmentation, in situ terminal deoxymucleotidyl transferase dUTP nick end labeling (TUNEL) was performed. The p53 expression was determined by immunohistochemical staining (IHCS). An average of 1000 nuclei was analyzed for TUNEL and p53 staining studies.

scholarly journals Association of arsenic-induced cardiovascular disease susceptibility with genetic polymorphisms

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mohammad Al-Forkan ◽  
Fahmida Binta Wali ◽  
Laila Khaleda ◽  
Md. Jibran Alam ◽  
Rahee Hasan Chowdhury ◽  
...  
Keyword(s):  
Heart Surgery ◽  
Cardiac Tissue ◽  
Tissue Injury ◽  
Open Heart Surgery ◽  
Inorganic Arsenic ◽  
Vital Role ◽  
Nucleotide Polymorphisms ◽  
Cross Sectional ◽  
Adjusted Analysis ◽  
Diabetes Status

AbstractInorganic arsenic (iAs) exposure has been reported to have an impact on cardiovascular diseases (CVD). However, there is not much known about the cardiac tissue injury of CVD patients in relation to iAs exposure and potential role of single nucleotide polymorphisms (SNPs) of genes related to iAs metabolism, oxidative stress, endothelial dysfunction and inflammation which may play important roles in such CVD cases. In this dual center cross-sectional study, based on the exclusion and inclusion criteria, we have recruited 50 patients out of 270, who came from known arsenic-affected and- unaffected areas of mainly Chittagong, Dhaka and Rajshahi divisions of Bangladesh and underwent open-heart surgery at the selected centers during July 2017 to June 2018. We found that the patients from arsenic affected areas contained significantly higher average iAs concentrations in their urine (6.72 ± 0.54 ppb, P = 0.028), nail (529.29 ± 38.76 ppb, P < 0.05) and cardiac tissue (4.83 ± 0.50 ppb, P < 0.05) samples. Patients’ age, sex, BMI, hypertension and diabetes status adjusted analysis showed that patients from arsenic-affected areas had significantly higher iAs concentration in cardiac tissue (2.854, 95%CI 1.017–8.012, P = 0.046) reflecting higher cardiac tissue injury among them (1.831, 95%CI 1.032–3.249, P = 0.039), which in turn allowed the analysis to assume that the iAs exposure have played a vital role in patients’ disease condition. Adjusted analysis showed significant association between urinary iAs concentration with AA (P = 0.012) and AG (P = 0.034) genotypes and cardiac iAs concentration with AA (P = 0.017) genotype of AS3MT rs10748835. The AG genotype of AS3MT rs10748835 (13.333 95%CI 1.280–138.845, P = 0.013), AA genotype of NOS3 rs3918181 (25.333 95%CI 2.065–310.757, P = 0.002), GG genotype of ICAM1 rs281432 (12.000 95%CI 1.325–108.674, P = 0.010) and AA genotype of SOD2 rs2758331 (13.333 95%CI 1.280–138.845, P = 0.013) were found significantly associated with CVD patients from arsenic-affected areas. Again, adjusted analysis showed significant association of AA genotype of AS3MT rs10748835 with CVD patients from arsenic affected areas. In comparison to the reference genotypes of the selected SNPs, AA of AS3MT 10748835, AG of NOS3 rs3918181 and AC of rs3918188, GG of ICAM1 rs281432, TT of VCAM1 rs3176867, AA of SOD2 rs2758331 and GT of APOE rs405509 significantly increased odds of cardiac tissue injury of CVD patients from arsenic affected areas. The results showed that the selected SNPs played a susceptibility role towards cardiac tissue iAs concentration and injury among CVD patients from iAs affected areas.

scholarly journals Oxygen Tension Modulates Inhibition of L-type Calcium Currents by Isoflurane in Human Atrial Cardiomyocytes

2007 ◽  
Vol 106 (4) ◽  
pp. 715-722
Author(s):  
Pascal Kowark ◽  
Rocco Hüneke ◽  
Eberhard Jüngling ◽  
Rolf Rossaint ◽  
Andreas Lückhoff
Keyword(s):  
Heart Surgery ◽  
Splice Variants ◽  
Open Heart Surgery ◽  
Decisive Role ◽  
Calcium Currents ◽  
Patch Clamp Technique ◽  
Human Cardiomyocytes ◽  
Atrial Cardiomyocytes ◽  
Whole Cell Patch Clamp ◽  
Wide Range

Background Myocardial L-type Ca(2+) currents (I(Ca,L)) are inhibited by isoflurane in the presence of a partial pressure of oxygen (P(O2)) of 150 mmHg. In guinea pig cardiomyocytes, I(Ca,L) are inhibited by reduced oxygen tensions. The authors therefore analyzed the effects of P(O2) on I(Ca,L) in human cardiomyocytes and the effects of isoflurane at reduced P(O2). Methods Atrial cardiomyocytes were prepared from specimens of patients undergoing open-heart surgery and superfused with either a high or a low P(O2) (150 or 12 +/- 1 mmHg) while I(Ca,L) were measured with the whole cell patch clamp technique. Results Basal I(Ca,L) were not changed by the P(O2) (range, 9-150 mmHg) at 21 degrees or 36 degrees C. The reducing agent 1,4-dithiothreitol (DTT) left I(Ca,L) unaffected, and the oxidizing agent 5,5'-dithio-bis(2-nitrobenzoic acid) (DTNB) irreversibly inhibited I(Ca,L). The P(O2) significantly affected the inhibition of I(Ca,L) by isoflurane (1 minimum alveolar concentration) that decreased I(Ca,L) by 17 +/- 2.0% at the high P(O2) but only by 5.8 +/- 2.9% (P = 0.037) at the low P(O2). The inhibition of I(Ca,L) by isoflurane was also significantly diminished (P = 0.018) by a low P(O2) when isoflurane effects at both P(O2) conditions were compared in the same cell. Conclusions In contrast to the situation in guinea pigs, basal I(Ca,L) in human atrial cardiomyocytes was not sensitive to acute P(O2) changes over a wide range. This might be explained by a lack of oxygen-sensitive splice variants of L-type calcium channel subunits. The P(O2), however, has a decisive role for the effects of isoflurane on I(Ca,L).

Evaluation of Cardiomyocyte Viability after Cardiac Tissue Incubated in Special Culture System

2000 ◽  
Vol 6 (S2) ◽  
pp. 620-621
Author(s):  
C. Wei ◽  
J Papadimitriou
Keyword(s):  
Culture System ◽  
Heart Surgery ◽  
Cardiac Tissue ◽  
Open Heart Surgery ◽  
Culture Conditions ◽  
Culture Period ◽  
Open Heart ◽  
Hypertrophic Response ◽  
Signaling Mechanisms ◽  
Apoptotic Effect

Cardiac myocytes maintained in cell culture develop hypertrophy both in response to mechanical loading as well as to receptor-mediated signaling mechanisms. However, it has been shown that the hypertrophic response to these stimuli may be modulated through effects of intercellular contact achieved by maintaining cells at different plating densities. We recently developed the new special tissue culture system to culture minced cardiac tissue and to evaluate the apoptotic effect of different agent in cardiomyocytes. After 24 hours culture period, different culture conditions and factors may damage the cardiomyocyte. Therefore, we performed different methods to evaluate the viability of cardiomyocyte in cardiac tissue with 24 hours culture period in our special culture system.Human cardiac atrial tissue was obtained from open-heart surgery (n=6). After cardiac tissue excision, the samples were immediately placed in oxygenated, nominally Ca2+-free Tyrode solution for transport to the laboratory. The time between excision and the beginning of laboratory processing was five to fifteen minutes.

Increasing Apoptosis-Related Gene Expression in Human Myocardium with Congestive Heart Failure

2000 ◽  
Vol 6 (S2) ◽  
pp. 628-629
Author(s):  
D. Xie ◽  
C. Wei
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Normal Subjects ◽  
Left Ventricular ◽  
Cardiac Tissues ◽  
Human Cardiomyocytes ◽  
Cycle Arrest ◽  
Induced Apoptosis ◽  
End Stage ◽  
Apoptosis Related Gene

Regulation of apoptosis involves a number of genes that can be classified into broad categories. These include genes that act as effectors of apoptosis, such as p53, c-myc, bax, p21- WAF, and genes that primarily suppress apoptosis, such as Bcl-2 gene family. These genes have been reported to be responsible for the modulation of certain stress induced apoptosis and cell cycle arrest.It has also been reported that apoptosis involved in cardiovascular diseases such as myocardial infarction, reperfusion injury, left ventricular hypertrophy, and hypertension. However, the expression of apoptosis-related genes in human cardiomyocytes in normal subjects and in patients with congestive heart failure (CHF) remains unclear. Therefore, the present study was designed to determine the expression and localization of apoptosis-related genes in human heart.Five normal subjects and five end-stage CHF human ventricular cardiac tissues were obtained from cardiac transplantation. The expression of p53, p21-WAF and Bcl-2 were determined by immunohistochemical staining (IHCS).

scholarly journals Hypoxia downregulates p53 but induces apoptosis and enhances expression of BAD in cultures of human syncytiotrophoblasts

2010 ◽  
Vol 299 (5) ◽  
pp. C968-C976 ◽  
Author(s):  
Baosheng Chen ◽  
Mark S. Longtine ◽  
Yoel Sadovsky ◽  
D. Michael Nelson
Keyword(s):  
Cell Death ◽  
Intrauterine Growth Restriction ◽  
Kinase Inhibitor ◽  
Primary Cultures ◽  
Hypoxia Inducible Factor ◽  
P53 Expression ◽  
Intrauterine Growth ◽  
Enhanced Expression ◽  
Induced Apoptosis ◽  
Dependent Pathway

Hypoxia is commonly assigned a role in the placental dysfunction characteristic of preeclampsia and intrauterine growth restriction. We previously showed that hypoxia upregulates p53 and enhances apoptosis in primary cultures of human cytotrophoblasts. Here we tested the hypothesis that hypoxia also induces apoptosis in syncytiotrophoblasts by upregulation of p53. Primary cultures of human cytotrophoblasts that had differentiated into syncytiotrophoblasts by 52 h were exposed for ≤24 h to 20% or <1% oxygen in the presence or absence of staurosporine or the p53 modulators nutlin-3, pifithrin-α, and pifithrin-μ. Proteins were detected by Western blot analysis or immunofluorescence. Compared with 20% oxygen, exposure of syncytiotrophoblasts to <1% oxygen upregulated hypoxia-inducible factor (HIF)-1α and rapidly downregulated p53. Activity of p53 in hypoxic syncytiotrophoblasts was reduced by the higher expression of the negative p53 regulator MDMX and by the reduction of phosphorylation of p53 at Ser392, which reduces p53 activity. Conversely, staurosporine, a kinase inhibitor, and nutlin-3, a drug that enhances p53 expression, both raised p53 levels and increased the rate of apoptosis in syncytiotrophoblasts compared with vehicle controls. Immunofluorescence staining showed p53 immunolocalized to both cytoplasm and nuclei of nutlin-3-exposed syncytiotrophoblasts. The hypoxia-induced apoptosis in syncytiotrophoblasts correlated with enhanced expression of the proapoptotic BAD and a reduced level of antiapoptotic BAD phosphorylated on Ser112. We surmise that cell death induced by extreme hypoxia in syncytiotrophoblasts follows a non-p53-dependent pathway, unlike that of a nonhypoxic stimulus and unlike hypoxic cytotrophoblasts. We speculate that downregulation of p53 activity in response to hypoxia reduces or eliminates the apoptosis transduced by the p53 pathway in syncytiotrophoblasts, thereby limiting cell death and maintaining the integrity of this critical villous component.

Angiotensin II Increases Apoptosis and Caspase-1 Expression in Human Myocardium

2000 ◽  
Vol 6 (S2) ◽  
pp. 630-631
Author(s):  
H. Song ◽  
S. W. Downing ◽  
C. Wei
Keyword(s):  
Angiotensin Ii ◽  
Receptor Antagonist ◽  
Heart Surgery ◽  
Cardiac Tissue ◽  
Open Heart Surgery ◽  
Cardiomyocyte Apoptosis ◽  
Tunel Staining ◽  
Caspase 1 ◽  
Potent Vasoconstrictor ◽  
Human Cardiac Tissue

Angiotensin II (AII) is a potent vasoconstrictor and mitogenic factor. The biological actions of All through AII receptors which include AT-1 and AT-2 receptors. However, the effects of AII on cardiomyocyte apoptosis and caspase expression remain controversial. Therefore, the current study was designed to investigate the actions of AII on human cardiomyocyte apoptosis and caspase-1 expression.Human cardiac tissue was obtained from open-heart surgery (n=6). The cardiac tissue was minced and incubated in the special tissue culture system for 24 hours in the absence or presence of AII (10-7 M). These studies were repeated with losartan (10-6 M, AT-1 receptor antagonist) and PD123319 (PD, 10-6 M, AT-2 receptor antagonist). To detect the DNA fragmentation, TUNEL staining and DNA gel analyses were performed. The caspase-1 expression was determined by immunohistochemical staining (IHCS). An average of 1000 nuclei was analyzed for both TUNEL and caspase-1 IHCS studies.

Enhanced Effective Fibrinolysis following the Neutralization of Heparin in Open Heart Surgery Increases the Risk of Post-Surgical Bleeding

1990 ◽  
Vol 63 (02) ◽  
pp. 241-245 ◽  
Author(s):  
Jørgen Gram ◽  
Thomas Janetzko ◽  
Jørgen Jespersen ◽  
Hans Dietrich Bruhn
Keyword(s):  
Blood Loss ◽  
Plasminogen Activator ◽  
Heart Surgery ◽  
Degradation Products ◽  
Open Heart Surgery ◽  
Tissue Type ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator ◽  
Chest Tube Drain ◽  
Median Blood Loss

SummaryThe tissue-type plasminogen activator related fibrinolytic system was studied in 24 patients undergoing cardiopulmonary bypass surgery. The degradation of fibrinogen and fibrin was followed during and after surgery by means of new sensitive and specific assays and the changes were related to the blood loss measured in the chest tube drain during the first 24 postoperative hours. Although tissue-type plasminogen activator was significantly released into the circulation during the period of extracor-poreal circulation (p <0.01), constantly low levels of fibrinogen degradation products indicated that a systemic generation of plasmin could be controlled by the naturally occurring inhibitors. Following extracorporeal circulation heparin was neutralized by protamine chloride, and in relation to the subsequent generation of fibrin, there was a short period with increased concentrations of fibrinogen degradation products (p <0.01) and a prolonged period of degradation of cross-linked fibrin, as detected by increased concentrations of D-Dimer until 24 h after surgery (p <0.01). Patients with a higher than the median blood loss (520 ml) in the chest tube drain had a significantly higher increase of D-Dimer than patients with a lower than the median blood loss (p <0.05).We conclude that the incorporation of tissue-type plasminogen activator into fibrin and the in situ activation of plasminogen enhance local fibrinolysis, thereby increasing the risk of bleeding in patients undergoing open heart surgery

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