Cardiac macrophages and apoptosis after myocardial infarction: effects of central MR blockade

2014 ◽  
Vol 307 (7) ◽  
pp. R879-R887 ◽  
Author(s):  
Naimeh Rafatian ◽  
Katherine V. Westcott ◽  
Roselyn A. White ◽  
Frans H. H. Leenen
Keyword(s):  
Myocardial Infarction ◽  
Time Course ◽  
Caspase 3 ◽  
Macrophage Infiltration ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Intracerebroventricular Infusion ◽  
Apoptosis And Inflammation ◽  
A Minor ◽  
The Brain ◽  
Active Caspase

After myocardial infarction (post-MI), inflammation and apoptosis contribute to progressive cardiac remodeling and dysfunction. Cardiac mineralocorticoid receptor (MR) and β-adrenergic signaling promote apoptosis and inflammation. Post-MI, MR activation in the brain contributes to sympathetic hyperactivity and an increase in cardiac aldosterone. In the present study, we assessed the time course of macrophage infiltration and apoptosis in the heart as detected by both terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and active caspase-3 immunostaining in both myocytes and nonmyocytes, as well as the effects of central MR blockade by intracerebroventricular infusion of eplerenone at 5 μg/day on peak changes in macrophage infiltration and apoptosis post-MI. Macrophage numbers were markedly increased in the infarct and peri-infarct zones and to a minor extent in the noninfarct part of the left ventricle at 10 days post-MI and decreased over the 3-mo study period. Apoptosis of both myocytes and nonmyocytes was clearly apparent in the infarct and peri-infarct areas at 10 days post-MI. For TUNEL, the increases persisted at 4 and 12 wk, but the number of active caspase-3-positive cells markedly decreased. Central MR blockade significantly decreased CD80-positive proinflammatory M1 macrophages and increased CD163-positive anti-inflammatory M2 macrophages in the infarct. Central MR blockade also reduced apoptosis of myocytes by 40–50% in the peri-infarct and to a lesser extent of nonmyocytes in the peri-infarct and infarct zones. These findings indicate that MR activation in the brain enhances apoptosis both in myocytes and nonmyocytes in the peri-infarct and infarct area post-MI and contributes to the inflammatory response.

scholarly journals Protective Effects of HBSP on Ischemia Reperfusion and Cyclosporine A Induced Renal Injury

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Yuanyuan Wu ◽  
Junlin Zhang ◽  
Feng Liu ◽  
Cheng Yang ◽  
Yufang Zhang ◽  
...  
Keyword(s):  
Cyclosporine A ◽  
Caspase 3 ◽  
Interstitial Fibrosis ◽  
Ischemia Reperfusion ◽  
Inflammatory Cells ◽  
Protective Effects ◽  
Tubulointerstitial Damage ◽  
Apoptosis And Inflammation ◽  
The Right ◽  
Active Caspase

Ischemia reperfusion (IR) and cyclosporine A (CsA) injuries are unavoidable in kidney transplantation and are associated with allograft dysfunction. Herein, the effect and mechanism of a novel tissue protective peptide, helix B surface peptide (HBSP) derived from erythropoietin, were investigated in a rat model. The right kidney was subjected to 45 min ischemia, followed by left nephrectomy and 2-week reperfusion, with or without daily treatment of CsA 25 mg/kg and/or HBSP 8 nmol/kg. Blood urea nitrogen was increased by CsA but decreased by HBSP at 1 week and 2 weeks, while the same changes were revealed in urinary protein/creatinine only at 2 weeks. HBSP also significantly ameliorated tubulointerstitial damage and interstitial fibrosis, which were gradually increased by IR and CsA. In addition, apoptotic cells, infiltrated inflammatory cells, and active caspase-3+ cells were greatly reduced by HBSP in the both IR and IR + CsA groups. The 17 kD active caspase-3 protein was decreased by HBSP in the IR and IR + CsA kidneys, with decreased mRNA only in the IR + CsA kidneys. Taken together, it has been demonstrated, for the first time, that HBSP effectively improved renal function and tissue damage caused by IR and/or CsA, which might be through reducing caspase-3 activation and synthesis, apoptosis, and inflammation.

Potent Therapy and Transcriptional Profile of Combined Erythropoietin Derived Peptide CHBP and Caspase-3 siRNA against Kidney Ischemia/Reperfusion Injury in mice

2020 ◽  
Author(s):  
Yuanyuan Wu ◽  
Weiwei Chen ◽  
Yufang Zhang ◽  
Aifen Liu ◽  
Cheng Yang ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Ischemia Reperfusion Injury ◽  
Early Stage ◽  
Synergistic Effects ◽  
Ischemia Reperfusion ◽  
Combined Treatment ◽  
Specific Treatment ◽  
Transcriptional Profile ◽  
Apoptosis And Inflammation ◽  
Active Caspase

Abstract Cause-specific treatment and timely diagnosis are still not available for acute kidney injury (AKI) apart from supportive therapy and serum creatinine measurement. A novel erythropoietin-derived cyclic helix B surface peptide (CHBP) protects kidneys against AKI with different causes, but the underlying mechanism is not fully defined. Herein, we investigated the transcriptional profile of renoprotection induced by CHBP and its potential synergistic effects with siRNA targeting caspase-3, an executing enzyme of apoptosis and inflammation, (CASP3siRNA) on ischemia/reperfusion (IR)-induced AKI. Utilizing a mouse model with 30-min renal bilateral ischemia and 48-h reperfusion, the renoprotection of CHBP or CASP3siRNA was demonstrated in renal function and structure, active caspase-3 and HMGB1 expression. Combined treatment of CHBP and CASP3siRNA further preserved kidney structure, and reduced active caspase-3 and HMGB1. Furthermore, differentially expressed genes (DEGs) were identified with fold change > 1.414 and P < 0.05. In IR kidneys, 281 DEGs induced by CHBP were mainly involved in promoting cell division and improving cellular function and metabolism (up-regulated STAT5B and SLC22A7). The additional administration of CASP3siRNA caused 504 and 418 DEGs in IR + CHBP kidneys with or without NCsiRNA, with 37 genes in common. These DEGs were associated with modulated apoptosis and inflammation (up-regulated BCL6, SLPI and SERPINA3M), and immunity, injury and microvascular homeostasis (up-regulated CFH and GREM1, and down-regulated ANGPTL2). This proof-of-effect study indicated the potent renoprotection of CASP3siRNA upon CHBP at the early stage of IR-induced AKI. Underlying genes, BCL6, SLPI, SERPINA3M, GREM1 and ANGPTL2, might be potential new biomarkers for clinical applications.

scholarly journals Catheter-Free Arrhythmia Ablation Using Scanned Proton Beams

2020 ◽  
Vol 13 (10) ◽  
Author(s):  
Atsushi Suzuki ◽  
Amanda J. Deisher ◽  
Maryam E. Rettmann ◽  
H. Immo Lehmann ◽  
Stephan Hohmann ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Proton Beam ◽  
Time Course ◽  
Caspase 3 ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Proton Beams ◽  
Atrioventricular Junction ◽  
Active Caspase

Background: Proton beam therapy offers radiophysical properties that are appealing for noninvasive arrhythmia elimination. This study was conducted to use scanned proton beams for ablation of cardiac tissue, investigate electrophysiological outcomes, and characterize the process of lesion formation in a porcine model using particle therapy. Methods: Twenty-five animals received scanned proton beam irradiation. ECG-gated computed tomography scans were acquired at end-expiration breath hold. Structures (atrioventricular junction or left ventricular myocardium) and organs at risk were contoured. Doses of 30, 40, and 55 Gy were delivered during expiration to the atrioventricular junction (n=5) and left ventricular myocardium (n=20) of intact animals. Results: In this study, procedural success was tracked by pacemaker interrogation in the atrioventricular junction group, time-course magnetic resonance imaging in the left ventricular group, and correlation of lesion outcomes displayed in gross and microscopic pathology. Protein extraction (active caspase-3) was performed to investigate tissue apoptosis. Doses of 40 and 55 Gy caused slowing and interruption of cardiac impulse propagation at the atrioventricular junction. In 40 left ventricular irradiated targets, all lesions were identified on magnetic resonance after 12 weeks, being consistent with outcomes from gross pathology. In the majority of cases, lesion size plateaued between 12 and 16 weeks. Active caspase-3 was seen in lesions 12 and 16 weeks after irradiation but not after 20 weeks. Conclusions: Scanned proton beams can be used as a tool for catheter-free ablation, and time-course of tissue apoptosis was consistent with lesion maturation.

scholarly journals Assessment of aflatoxin B1 myocardial toxicity in rats: mitochondrial damage and cellular apoptosis in cardiomyocytes induced by aflatoxin B1

2017 ◽  
Vol 45 (3) ◽  
pp. 1015-1023 ◽  
Author(s):  
Junhua Ge ◽  
Haichu Yu ◽  
Jian Li ◽  
Zhexun Lian ◽  
Hongjing Zhang ◽  
...  
Keyword(s):  
Aflatoxin B1 ◽  
Caspase 3 ◽  
Cardiac Tissue ◽  
Myocardial Cell ◽  
Heart Tissue ◽  
Mitochondrial Damage ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Toxic Activity ◽  
Enhanced Expression ◽  
Active Caspase

Objective The number of deaths from heart disease is increasing worldwide. Aflatoxin B1 (AFB1), a toxin produced by the fungi Aspergillus flavus and Aspergillus parasiticus, is frequently detected in improperly processed/stored human food products. While AFB1 hepatotoxicity and carcinogenic properties have been well addressed, its myocardial toxicity is poorly documented. This study aimed to investigate myocardial toxic activity of AFB1. Methods Ten rats were fed with AFB1 at a dose that did not result in acute toxic reactions for 30 days and 10 vehicle-fed rats served as controls. Transmission electron microscopy was used to assess mitochondrial damage in cardiomyocytes. The terminal deoxynucleotidyl transferase-mediated UTP nick-end labelling assay was performed to detect apoptosis of cardiomyocytes. Western blotting was performed to measure apoptotic proteins (i.e., active caspase-3, Bax, and Bcl-2) in heart tissue. Results AFB1 treatment resulted in mitochondrial membrane disruption and disorganization of cristae, which are indicators of mitochondrial damage. Myocardial cell apoptosis was significantly higher after AFB1 treatment (22.07% ± 3.29%) compared with controls (6.27% ± 2.78%, P < 0.05). AFB1 treatment enhanced expression of active caspase-3, Bax, and Bcl-2 in cardiac tissue. Conclusion Various adverse effects are exerted by AFB1 on the heart, indicating AFB1 myocardial toxicity.

The interrelationship between BDNF and its precursor and the level of active caspase-3 in the brain regions of neonatal rats

2012 ◽  
Vol 6 (4) ◽  
pp. 260-264 ◽  
Author(s):  
V. V. Muzyka ◽  
P. N. Men’shanov ◽  
A. V. Bannova ◽  
N. N. Dygalo
Keyword(s):  
Caspase 3 ◽  
Brain Regions ◽  
Neonatal Rats ◽  
The Brain ◽  
Active Caspase

Prenatally administered dexamethasone impairs folliculogenesis in spiny mouse offspring

2016 ◽  
Vol 28 (7) ◽  
pp. 1038 ◽  
Author(s):  
Monika Hułas-Stasiak ◽  
Piotr Dobrowolski ◽  
Ewa Tomaszewska
Keyword(s):  
Caspase 3 ◽  
Follicular Development ◽  
Treated Group ◽  
Spiny Mouse ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Follicular Atresia ◽  
Dexamethasone Treatment ◽  
Primordial Follicles ◽  
Acomys Cahirinus ◽  
Active Caspase

This study was designed to determine whether prenatal dexamethasone treatment has an effect on follicular development and atresia in the ovary of spiny mouse (Acomys cahirinus) offspring. Dexamethasone (125 µg kg–1 bodyweight per day) was administered to pregnant spiny mice from Day 20 of gestation to parturition. The processes of follicle loss were analysed using classical markers of apoptosis (terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling reaction, active caspase-3) and autophagy (Lamp1). The present study indicated that dexamethasone reduced the pool of healthy primordial follicles. Moreover, the oocytes from these follicles showed intensive caspase-3 and Lamp1 staining. Surprisingly, dexamethasone caused an increase in the number of secondary follicles; however, most of these follicles were characterised by extensive degeneration of the oocyte and caspase-3 and Lamp1 labelling. Western-blot analysis indicated that the glucocorticoid receptor as well as apoptosis and autophagy markers were more strongly expressed in the DEX-treated group than in the control. On the basis of these findings, we have concluded that dexamethasone impairs spiny mouse folliculogenesis and enhances follicular atresia through induction of autophagy or combined autophagy and apoptosis.

scholarly journals Involvement of Caspase-3 in Cell Death after Hypoxia–Ischemia Declines during Brain Maturation

2000 ◽  
Vol 20 (9) ◽  
pp. 1294-1300 ◽  
Author(s):  
Bing R. Hu ◽  
Chun Li Liu ◽  
Yibing Ouyang ◽  
Klas Blomgren ◽  
Bo K. Siesjö
Keyword(s):  
Cell Death ◽  
Caspase 3 ◽  
Brain Maturation ◽  
Minor Role ◽  
Artery Ligation ◽  
Adult Rats ◽  
Hypoxia Ischemia ◽  
High Level ◽  
A Minor ◽  
Active Caspase

The involvement of caspase-3 in cell death after hypoxia–ischemia (HI) was studied during brain maturation. Unilateral HI was produced in rats at postnatal day 7 (P7), 15 (P15), 26 (P26), and 60 (P60) by a combination of left carotid artery ligation and systemic hypoxia (8% O2). Activation of caspase-3 and cell death was examined in situ by high-resolution confocal microscopy with anti-active caspase-3 antibody and propidium iodide and by biochemical analysis. The active caspase-3 positive neurons were composed of more than 90% HI damaged striatal and neocortical neurons in P7 pups, but that number was reduced to approximately 65% in striatum and 34% in the neocortex of P15 pups, and approximately 26% in striatum and 2% in neocortex of P26 rats. In P60 rats, less than 4% of the damaged neurons in striatum and less than 1% in neocortex were positive for active caspase-3. Western blot analysis demonstrated that the level of inactive caspase-3 in normal forebrain tissue gradually declined from a high level in young pups to very low levels in adult rats. Concomitantly, HI-induced active caspase-3 was reduced from a relatively high level in P7, to moderate levels in P15 and P26, to a barely detectable level in P60 rats. The authors conclude that the involvement of caspase-3 in the pathogenesis of cell death after HI declines during neuronal maturation. The authors hypothesize that caspase-3 may play a major role in cell death in immature neurons but a minor role in cell death in mature neurons after brain injury.

Central nervous system toxicity after acute oral formaldehyde exposure in rabbits

2014 ◽  
Vol 33 (11) ◽  
pp. 1141-1149 ◽  
Author(s):  
S Arici ◽  
S Karaman ◽  
S Dogru ◽  
S Cayli ◽  
A Arici ◽  
...  
Keyword(s):  
Nervous System ◽  
Brain Tissue ◽  
Caspase 3 ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Oral Exposure ◽  
Rabbit Brain ◽  
Control Group ◽  
Urogenital System ◽  
Tissue Samples ◽  
Active Caspase

Formaldehyde (FA) is one of the most widely used chemical compounds in industrial field. It is described as toxic, particularly to the nervous system, the urogenital system, and the respiratory tracts. In this study, we determined the effects of acute oral exposure to FA in rabbit brain tissue. A total of 16 rabbits were selected and divided into 2 groups: formaldehyde group (group F) and control group (group C). FA was administered to group F at a rate of 40 mg/kg/day via a nasogastric tube for 5 days. Saline was similarly administered to the eight controls. All the animals were euthanized after 5 days of exposure, and brain tissue samples were collected in 10% neutral formalin and embedded in paraffin. To investigate the effects of FA on the apoptotic process, we examined active caspase-3, Bax, and Bcl-2 immunohistochemical expression and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate –biotin nick-end labeling (TUNEL) reactivity in the rabbit brains. In addition, glial fibrillary acidic protein (GFAP) was biochemically assessed in brain tissue samples for neurotoxicity. We found that FA treatment caused a significant decrease in Bcl-2 expression and an increase in active caspase-3 and Bax expressions as well as an increase in the number of TUNEL-positive apoptotic cells. The GFAP level was found to be significantly higher in group F. In conclusion, acute oral exposure to FA caused DNA damage, apoptosis, and neuronal injury in the rabbit brains.

scholarly journals Time-Course of the Effects of QSYQ in Promoting Heart Function in Ameroid Constrictor-Induced Myocardial Ischemia Pigs

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Qi Qiu ◽  
Yang Lin ◽  
Cheng Xiao ◽  
Chun Li ◽  
Yong Wang ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Time Course ◽  
Caspase 3 ◽  
Heart Function ◽  
Cardiac Injury ◽  
Myocardial Tissue ◽  
Therapeutic Effects ◽  
Ang Ii ◽  
Histological Changes ◽  
Active Caspase

We aim to investigate the therapeutic effects of QSYQ on a pig myocardial ischemia (MI) model and to determine its mechanism of action. The MI model was induced by Ameroid constriction of the left anterior descending coronary (LAD) in Ba-Ma miniature pigs. Four groups were created: model group, digoxin group, QSYQ group, and sham-operated group. Heart function, Ang II, CGMP, TXB2, BNP, and cTnT were evaluated before (3 weeks after operation: 0 weeks) and at 2, 4, and 8 weeks after drug administration. After 8 weeks of administration, the pigs were sacrificed for cardiac injury measurements. Pigs with MI showed obvious histological changes, including BNP, cTnT, Ang II, CGRP, TXB2, and ET, deregulated heart function, and increased levels of apoptotic cells in myocardial tissue. Treatment with QSYQ improved cardiac remodeling by counteracting those events. The administration of QSYQ was accompanied by a restoration of heart function and of the levels of Ang II, CGRP, TXB2, ET BNP, and cTnT. In addition, QSYQ attenuated administration, reduced the apoptosis, and decreased the level of TNF-αand active caspase-3. In conclusion, administration of QSYQ could attenuate Ameroid constrictor induced myocardial ischemia, and TNF-αand active caspase-3 seemed to be the critical potential target of QSYQ.

Reduced apoptosis in term placentas from gestational diabetic pregnancies

2013 ◽  
Vol 4 (3) ◽  
pp. 256-265 ◽  
Author(s):  
L. Belkacemi ◽  
S. Kjos ◽  
D. M. Nelson ◽  
M. Desai ◽  
M. G. Ross
Keyword(s):  
Body Weight ◽  
Maternal Age ◽  
Caspase 3 ◽  
Placental Tissue ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Diabetic Mellitus ◽  
Neonatal Birth Weight ◽  
Increased Risk ◽  
The Mean ◽  
Active Caspase

Gestational diabetic mellitus (GDM) pregnancies have an increased risk of macrosomic infants and large placental mass, though the mechanisms explaining each of these is uncertain. We sought to evaluate the contribution of apoptosis to placental size and the expression of glucose transporters (SLC2A) in GDM pregnancies. Maternal age and pre-pregnancy body weight were documented. Newborn weights were recorded after delivery. Placentas 37–40-week gestation from control patients (no pregnancy complication) (n = 5), or with GDM (n = 5) were weighed immediately after delivery. Villous samples (4 mm diameter) were collected and divided into specimens; one was fixed in 4% paraformaldehyde for immunostaining using terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling (TUNEL) and activated caspase-3. The other specimen was snap frozen in liquid nitrogen and stored at −80°C for active caspase-3, poly(ADP-ribose) polymerase (PARP), SLC2A1 and SLC2A3 gene expression analysis. Our results showed that maternal age and pre-pregnancy body weight were significantly higher in the GDM group when compared with those from the controls (P < 0.05). The mean neonatal birth weight and placenta weight were significantly higher in the GDM group compared with that from the controls (P < 0.05). The apoptotic index of placentas (0.05 ± 0.01 v. 0.17 ± 0.04, P < 0.04), active caspase-3 polypeptide fragments and PARP protein were significantly decreased in GDM placentas as compared with controls. Further, the level of placental SLC2A1 protein expression was ∼3-fold higher in GDM placentas. Our results suggest that reduced apoptosis in GDM placentas may contribute to increased placental tissue, which together with enhanced SLC2A1 expression, could play a role in fetal macrosomia.

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