scholarly journals CTRP9 Mediates Protective Effects in Cardiomyocytes via AMPK- and Adiponectin Receptor-Mediated Induction of Anti-Oxidant Response

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1229
Author(s):  
Bernd Niemann ◽  
Ling Li ◽  
Dorothee Siegler ◽  
Benedikt H. Siegler ◽  
Fabienne Knapp ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Direct Interaction ◽  
Left Ventricular ◽  
Cardiac Cells ◽  
Adiponectin Receptor ◽  
Protective Effects ◽  
Necrosis Factor Alpha ◽  
Anti Oxidant ◽  
Cardioprotective Effects ◽  
The Right

The C1q/tumor necrosis factor-alpha-related protein 9 (CTRP9) has been reported to exert cardioprotective effects, but its role in the right ventricle (RV) remains unclear. To investigate the role of CTRP9 in RV hypertrophy and failure, we performed pulmonary artery banding in weanling rats to induce compensatory RV hypertrophy seven weeks after surgery and RV failure 22 weeks after surgery. CTRP9 expression, signal transduction and mechanisms involved in protective CTRP9 effects were analyzed in rat and human RV tissue and cardiac cells. We demonstrate that CTRP9 was induced during compensatory RV hypertrophy but almost lost at the stage of RV failure. RV but not left ventricular (LV) cardiomyocytes or RV endothelial cells demonstrated increased intracellular reactive oxygen species (ROS) and apoptosis activation at this stage. Exogenous CTRP9 induced AMP-activated protein kinase (AMPK)-dependent transcriptional activation of the anti-oxidant thioredoxin-1 (Trx1) and superoxide dismutase-2 (SOD2) and reduced phenylephrine-induced ROS. Combined knockdown of adiponectin receptor-1 (AdipoR1) and AdipoR2 or knockdown of calreticulin attenuated CTRP9-mediated anti-oxidant effects. Immunoprecipitation showed an interaction of AdipoR1 with AdipoR2 and the co-receptor T-cadherin, but no direct interaction with calreticulin. Thus, CTRP9 mediates cardioprotective effects through inhibition of ROS production induced by pro-hypertrophic agents via AMPK-mediated activation of anti-oxidant enzymes.

scholarly journals Dexrazoxane preferentially mitigates doxorubicin cardiotoxicity in female children with sarcoma

Open Heart ◽  
2019 ◽  
Vol 6 (1) ◽  
pp. e001025 ◽  
Author(s):  
Hari K Narayan ◽  
Mary E Putt ◽  
Nikitha Kosaraju ◽  
Alejandro Paz ◽  
Shivani Bhatt ◽  
...  
Keyword(s):  
Circumferential Strain ◽  
Wall Stress ◽  
Left Ventricular ◽  
High Dose ◽  
Protective Effects ◽  
Cavity Size ◽  
Linear Regression Models ◽  
Cardioprotective Effects ◽  
And Function

ObjectiveWe sought to determine how sex and dexrazoxane therapy influence cardiac remodelling in children with sarcoma receiving high-dose doxorubicin.MethodsIn a retrospective cohort of 85 children with sarcoma receiving high-dose doxorubicin, echocardiography measures prior to, early after (within 6 months of doxorubicin completion) and 1 – 2 years after doxorubicin completion were quantified. At each follow-up visit, multivariable, propensity-adjusted linear regression models evaluated dexrazoxane’s effects on changes in left ventricular (LV) shortening fraction (SF), structure, strain and wall stress for subgroups divided by sex. Likelihood ratio tests assessed the interaction between sex and dexrazoxane in determining these changes.ResultsEarly after doxorubicin completion, males not treated with dexrazoxane (n = 15) developed increased cavity size and diminished circumferential strain; females (n = 8) developed diminished SF and strain indices, and increased cavity size and wall stress. With dexrazoxane, males (n = 33) demonstrated less deterioration in circumferential strain by 3.4% (95% CI 0.01 to 6.8), and females (n = 29) demonstrated less reduction in SF by 5.7% (95% CI 2.1 to 9.3), and had mitigation of increases in cavity size and wall stress. In interaction analyses, females had greater protection with dexrazoxane with regard to SF (p = 0.019) and cavity size in diastole (p = 0.002) and systole (p ≤ 0.001). These findings largely persisted 1 – 2 years after doxorubicin therapy.ConclusionsEarly, sustained alterations in LV structure and function occur in children with sarcoma after high-dose doxorubicin, with adverse changes and protective effects of dexrazoxane more pronounced in females as compared with males. Dexrazoxane may have sex-specific cardioprotective effects.

scholarly journals Characterization of mechanisms involved in transrepression of NF-kappa B by activated glucocorticoid receptors.

1995 ◽  
Vol 15 (2) ◽  
pp. 943-953 ◽  
Author(s):  
R I Scheinman ◽  
A Gualberto ◽  
C M Jewell ◽  
J A Cidlowski ◽  
A S Baldwin
Keyword(s):  
Gene Expression ◽  
Hela Cells ◽  
Transcriptional Activation ◽  
Glucocorticoid Receptors ◽  
Interleukin 1 ◽  
Direct Interaction ◽  
Significant Loss ◽  
Nf Kappa B ◽  
Necrosis Factor Alpha ◽  
Important Regulator

Glucocorticoids are potent immunosuppressants which work in part by inhibiting cytokine gene transcription. We show here that NF-kappa B, an important regulator of numerous cytokine genes, is functionally inhibited by the synthetic glucocorticoid dexamethasone (DEX). In transfection experiments, DEX treatment in the presence of cotransfected glucocorticoid receptor (GR) inhibits NF-kappa B p65-mediated gene expression and p65 inhibits GR activation of a glucocorticoid response element. Evidence is presented for a direct interaction between GR and the NF-kappa B subunits p65 and p50. In addition, we demonstrate that the ability of p65, p50, and c-rel subunits to bind DNA is inhibited by DEX and GR. In HeLa cells, DEX activation of endogenous GR is sufficient to block tumor necrosis factor alpha or interleukin 1 activation of NF-kappa B at the levels of both DNA binding and transcriptional activation. DEX treatment of HeLa cells also results in a significant loss of nuclear p65 and a slight increase in cytoplasmic p65. These data reveal a second mechanism by which NF-kappa B activity may be regulated by DEX. We also report that RU486 treatment of wild-type GR and DEX treatment of a transactivation mutant of GR each can significantly inhibit p65 activity. In addition, we found that the zinc finger domain of GR is necessary for the inhibition of p65. This domain is also required for GR repression of AP-1. Surprisingly, while both AP-1 and NF-kappa B can be inhibited by activated GR, synergistic NF-kappa B/AP-1 activity is largely unaffected. These data suggest that NF-kappa B, AP-1, and GR interact in a complex regulatory network to modulate gene expression and that cross-coupling of NF-kappa B and GR plays an important role in glucocorticoid-mediated repression of cytokine transcription.

End-systolic and end-diastolic ventricular interaction

1986 ◽  
Vol 251 (5) ◽  
pp. H1062-H1075 ◽  
Author(s):  
B. K. Slinker ◽  
S. A. Glantz
Keyword(s):  
Right Ventricular ◽  
Interventricular Septum ◽  
Systolic Pressure ◽  
Direct Interaction ◽  
Ventricular Volume ◽  
Left Ventricular ◽  
Physiological Mechanisms ◽  
In Series ◽  
The Right ◽  
Transient And Steady State

Right ventricular volume affects left ventricular volume via direct interaction across the interventricular septum and series interaction because the right and left hearts are connected in series through the lungs. Because it is difficult to sort out complex physiological mechanisms in the intact circulation, the relative importance of these two effects is unknown. We used statistical analyses of transient changes in left and right ventricular pressures and dimensions following pulmonary artery and venae caval constrictions to separate and quantitate the direct (immediate) from the series (delayed) interaction effects on left ventricular size at end systole and end diastole. With the pericardium closed, direct interaction was one-half as important as series interaction at end diastole and was one-third as important at end systole. With the pericardium removed, direct interaction was one-fifth as important as series interaction at end diastole and one-sixth as important at end systole. These results suggest that differences between transient and steady-state end-systolic pressure-volume relationships are largely explained by direct interaction and that direct end-systolic interaction is important for maintaining balanced right and left heart outputs.

Mechanism of decreased adenosine protection in reperfusion injury of aging rats

2000 ◽  
Vol 279 (1) ◽  
pp. H329-H338 ◽  
Author(s):  
Feng Gao ◽  
Theodore A. Christopher ◽  
Bernard L. Lopez ◽  
Eitan Friedman ◽  
Guoping Cai ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Protective Effects ◽  
No Release ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Cardioprotective Effects ◽  
Myocardial Ischemia Reperfusion

The purpose of this study was to determine whether the protective effects of adenosine on myocardial ischemia-reperfusion injury are altered with age, and if so, to clarify the mechanisms that underlie this change related to nitric oxide (NO) derived from the vascular endothelium. Isolated perfused rat hearts were exposed to 30 min of ischemia and 60 min of reperfusion. In the adult hearts, administration of adenosine (5 μmol/l) stimulated NO release (1.06 ± 0.19 nmol · min−1 · g−1, P < 0.01 vs. vehicle), increased coronary flow, improved cardiac functional recovery (left ventricular developed pressure 79 ± 3.8 vs. 57 ± 3.1 mmHg in vehicle, P < 0.001; maximal rate of left ventricular pressure development 2,385 ± 103 vs. 1,780 ± 96 in vehicle, P < 0.001), and reduced myocardial creatine kinase loss (95 ± 3.9 vs. 159 ± 4.6 U/100 mg protein, P < 0.01). In aged hearts, adenosine-stimulated NO release was markedly reduced (+0.42 ± 0.12 nmol · min−1 · g−1 vs. vehicle), and the cardioprotective effects of adenosine were also attenuated. Inhibition of NO production in the adult hearts significantly decreased the cardioprotective effects of adenosine, whereas supplementation of NO in the aged hearts significantly enhanced the cardioprotective effects of adenosine. The results show that the protective effects of adenosine on myocardial ischemia-reperfusion injury are markedly diminished in aged animals, and that the loss in NO release in response to adenosine may be at least partially responsible for this age-related alteration.

scholarly journals Anti-Oxidant and Anti-Inflammatory Effects of Lipopolysaccharide from Rhodobacter sphaeroides against Ethanol-Induced Liver and Kidney Toxicity in Experimental Rats

Molecules ◽  
2021 ◽  
Vol 26 (24) ◽  
pp. 7437
Author(s):  
Eman T. Mehanna ◽  
Al-Shimaa A. Ali ◽  
Fatma El-Shaarawy ◽  
Noha M. Mesbah ◽  
Dina M. Abo-Elmatty ◽  
...  
Keyword(s):  
Rhodobacter Sphaeroides ◽  
Iron Homeostasis ◽  
Kidney Injury ◽  
Control Group ◽  
Protective Effects ◽  
Necrosis Factor Alpha ◽  
Hepcidin Expression ◽  
Tnf Α ◽  
Anti Oxidant ◽  
Anti Inflammatory

This study aimed to investigate the protective effects of lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS) against ethanol-induced hepatotoxicity and nephrotoxicity in experimental rats. The study involved an intact control group, LPS-RS group, two groups were given ethanol (3 and 5 g/kg/day) for 28 days, and two other groups (LPS-RS + 3 g/kg ethanol) and (LPS-RS + 5 g/kg ethanol) received a daily dose of LPS-RS (800 μg/kg) before ethanol. Ethanol significantly increased the expression of nuclear factor kappa B (NF-κB) and levels of malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in the liver tissue and decreased anti-oxidant enzymes. Hepcidin expression was downregulated in the liver, with increased serum levels of ferritin and iron. Prior-administration of LPS-RS alleviated the increase in oxidative stress and inflammatory markers, and preserved iron homeostasis markers. In the kidney, administration of ethanol caused significant increase in the expression of NF-κB and the levels of TNF-α and kidney injury markers; whereas LPS-RS + ethanol groups had significantly lower levels of those parameters. In conclusion; this study reports anti-oxidant, anti-inflammatory and iron homeostasis regulatory effects of the toll-like receptor 4 (TLR4) antagonist LPS-RS against ethanol induced toxicity in both the liver and the kidney of experimental rats.

Effective protection by NHE-1 inhibition in ischemic and reperfused heart under preconditioning blockade

2003 ◽  
Vol 284 (3) ◽  
pp. H798-H803 ◽  
Author(s):  
James V. Haist ◽  
Claire N. Hirst ◽  
Morris Karmazyn
Keyword(s):  
Ischemic Preconditioning ◽  
Channel Blocker ◽  
Left Ventricular ◽  
Cardiac Cells ◽  
Protective Effects ◽  
Effective Protection ◽  
Intact Cells ◽  
Rat Hearts ◽  
Developed Pressure ◽  
Isolated Rat

We compared the protective effects of ischemic preconditioning (IPC) and the Na+/H+ exchanger-1 (NHE-1) inhibitor cariporide in isolated rat hearts subjected to global ischemia (45 or 90 min) and 30-min reperfusion and determined the protective effects of cariporide under IPC blockade with the mitochondrial ATP-sensitive K+ channel blocker 5-hydroxydecanoate (5-HD). With 45-min ischemia, both IPC and cariporide equally increased maximum recovery of left ventricular developed pressure twofold ( P < 0.05), although recovery was significantly greater with cariporide for the first 15 min of reperfusion. 5-HD almost completely blocked the protective effects of IPC on recovery but had no influence on the salutary effects of cariporide. With 90-min ischemic control, recovery was only 3% of preischemia and was unaffected by IPC, although cariporide increased recovery to ∼30% ( P < 0.05). This was associated with a 37% preservation of viable cardiac cells, whereas no structurally intact cells were found in either IPC or control hearts. Our study shows that NHE-1 inhibition is a more effective cardioprotective strategy than IPC in this model, possibly because of enhanced myocyte salvage, and because protection by NHE-1 inhibition is completely unaffected by IPC blockade with 5-HD.

Enteral Lactoferrin Administration Attenuates Myocardial Ischemia-Reperfusion Injury in an Isolated Rat Heart Model

2020 ◽  
Author(s):  
Keisuke Omiya ◽  
Yosuke Nakadate ◽  
Takeshi Oguchi ◽  
Tamaki Sato ◽  
Toru Matsuoka ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Isolated Rat Heart ◽  
Stunned Myocardium ◽  
Control Group ◽  
Protective Effects ◽  
Pressure Development ◽  
Cardioprotective Effects ◽  
Myocardial Ischemia Reperfusion

Abstract Background While lactoferrin, an iron-binding glycoprotein, has protective effects on intestinal and cerebral ischemia-reperfusion injuries, its cardioprotective effects against stunned myocardium are unknown. This study aimed to test the hypothesis that lactoferrin has cardioprotective effects against stunned myocardium. Methods Rat hearts were perfused using the Langendorff system, and two experiments were performed. In experiment 1, the hearts were divided into the enteral lactoferrin (E-LF) 7.5 m, 15 m, 30 m, and 60 m groups, where lactoferrin (1000 mg/kg) was administered enterally for 7.5, 15, 30, and 60 min, respectively, before perfusion; and a control group, where saline was administered 30 min before perfusion. In experiment 2, hearts were allocated to the perfusate lactoferrin (P-LF) 15 and 100 groups, where 15 mg/L and 100 mg/L lactoferrin were respectively added to the perfusate, and a control group. Each group was perfused for 20 min prior to 15 min of no-flow ischemia with pacing, followed by 20 min of reperfusion. The primary outcome was the maximum left ventricular derivative of pressure development (LV dP/dt max) 15 min after reperfusion. Myocardial phospho-protein kinase B (p-Akt) was assayed by western blotting. Results LV dP/dt max in the E-LF 15 m and 30 m groups was significantly higher than in the control group. In the second experiment, there were no significant differences in LV dP/dt max. Myocardial p-Akt was not significantly activated in any lactoferrin group. Conclusion Cardio-protection was observed with enteral but not parenteral lactoferrin administration, and myocardial p-Akt was not involved in this effect.

Glutamine Is Cardioprotective in Patients with Ischemic Heart Disease following Cardiopulmonary Bypass

2011 ◽  
Vol 14 (6) ◽  
pp. 384 ◽  
Author(s):  
Vladimir V. Lomivorotov ◽  
Sergey M. Efremov ◽  
Vladimir A. Shmirev ◽  
Dmitry N. Ponomarev ◽  
Vladimir N. Lomivorotov ◽  
...  
Keyword(s):  
Heart Disease ◽  
Placebo Group ◽  
Cardiopulmonary Bypass ◽  
Ischemic Heart Disease ◽  
Troponin I ◽  
Left Ventricular ◽  
Ischemic Heart ◽  
Left Ventricular Ejection ◽  
Study Group ◽  
Cardioprotective Effects

<p><b>Background:</b> The aim of the present study was to investigate the cardioprotective effects of the perioperative use of N(2)-L-alanyl-L-glutamine (GLN) in patients with ischemic heart disease (IHD) who undergo their operations under cardiopulmonary bypass (CPB).</p><p><b>Methods:</b> This double-blind, placebo-controlled, randomized study included 50 patients who underwent cardiac surgery with CPB. Exclusion criteria were a left ventricular ejection fraction <50%, diabetes mellitus, <3 months since the onset of myocardial infarction, and emergency surgery. Patients in the study group (n = 25) received 0.4 g/kg GLN (Dipeptiven, 20% solution) per day. Patients in the control group (n = 25) were administered a placebo (0.9% NaCl). The primary end point was the dynamics of troponin I at the following stages: (1) prior to anesthesia, (2) 30 minutes after CPB, (3) 6 hours after CPB, (4) 24 hours after surgery, and (5) 48 hours after surgery. Secondary end points included measurements of hemodynamics with a Swan-Ganz catheter.</p><p><b>Results:</b> On the first postoperative day after the surgery, the median troponin I level was significantly lower in the study group than in the placebo group: 1.280 ng/mL (interquartile range [IQR], 0.840-2.230 ng/mL) versus 2.410 ng/mL (IQR, 1.060-6.600 ng/mL) (<i>P</i> = .035). At 4 hours after cardiopulmonary bypass (CPB), the median cardiac index was higher in the patients in the study group: 2.58 L/min per m<sup>2</sup> (IQR, 2.34-2.91 L/min per m<sup>2</sup>) versus 2.03 L/min per m<sup>2</sup> (IQR, 1.76-2.32 L/min per m<sup>2</sup>) (<i>P</i> = .002). The median stroke index also was higher in the patients who received GLN: 32.8 mL/m<sup>2</sup> (IQR, 27.8-36.0 mL/m<sup>2</sup>) versus 26.1 mL/m<sup>2</sup> (IQR, 22.6-31.8 mL/m<sup>2</sup>) (<i>P</i> = .023). The median systemic vascular resistance index was significantly lower in the study group than in the placebo group: 1942 dyn�s/cm<sup>5</sup> per m<sup>2</sup> (IQR, 1828-2209 dyn�s/cm<sup>5</sup> per m<sup>2</sup>) versus 2456 dyn�s/cm<sup>5</sup> per m<sup>2</sup> (IQR, 2400-3265 dyn�s/cm<sup>5</sup> per m<sup>2</sup>) (<i>P</i> = .001).</p><p><b>Conclusion:</b> Perioperative administration of GLN during the first 24 hours has cardioprotective effects in IHD patients following CPB. This technique enhances the troponin concentration at 24 hours after surgery and is associated with improved myocardial function.</p>

Prevalence and Localization of Hibernating Myocardium Among Patients with Left Ventricular Dysfunction

2019 ◽  
Vol 15 (9) ◽  
pp. 884-889
Author(s):  
Emine Acar ◽  
Ayşegül Aksu ◽  
Gökmen Akkaya ◽  
Gamze Çapa Kaya
Keyword(s):  
Scar Tissue ◽  
Left Ventricular ◽  
Hibernating Myocardium ◽  
Circumflex Artery ◽  
Irrigation Area ◽  
Left Circumflex Artery ◽  
Pet Ct ◽  
Perfusion Defects ◽  
The Right ◽  
Fdg Pet Ct

Objective: This study evaluated how much of the myocardium was hibernating in patients with left ventricle dysfunction and/or comorbidities who planned to undergo either surgical or interventional revascularization. Furthermore, this study also identified which irrigation areas of the coronary arteries presented more scar and hibernating tissue. Methods: At rest, Tc-99m MIBI SPECT and cardiac F-18 FDG PET/CT images collected between March 2009 and September 2016 from 65 patients (55 men, 10 women, mean age 64±12) were retrospectively analyzed in order to evaluate myocardial viability. The areas with perfusion defects that were considered metabolic were accepted as hibernating myocardium, whereas areas with perfusion defects that were considered non-metabolic were accepted as scar tissue. Results: Perfusion defects were observed in 26% of myocardium, on average 48% were associated with hibernation whereas other 52% were scar tissue. In the remaining Tc-99m MIBI images, perfusion defects were observed in the following areas in the left anterior descending artery (LAD; 31%), in the right coronary artery (RCA; 23%) and in the Left Circumflex Artery (LCx; 19%) irrigation areas. Hibernation areas were localized within the LAD (46%), LCx (54%), and RCA (64%) irrigation areas. Scar tissue was also localized within the LAD (54%), LCx (46%), and RCA (36%) irrigation areas. Conclusion: Perfusion defects are thought to be the result of half hibernating tissue and half scar tissue. The majority of perfusion defects was observed in the LAD irrigation area, whereas hibernation was most often observed in the RCA irrigation area. The scar tissue development was more common in the LAD irrigation zone.

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