Low-Dose Endotoxin Induces Late Preconditioning, Increases Peroxynitrite Formation, and Activates STAT3 in the Rat Heart

Pipicz, Márton; Kocsis, Gabriella F.; Sárváry-Arantes, László; Bencsik, Péter; Varga, Zoltán V.; Ferdinándy, Péter; Csont, Tamás

doi:10.3390/molecules22030433

Cited by 10 publications

(7 citation statements)

References 54 publications

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“…Although enhanced peroxynitrite formation contributes to the pathophysiology of cardiovascular diseases, it was demonstrated that nanomolar concentrations of peroxynitrite inhibit leukocyte-endothelial cell interaction, which improves postischemic myocardial function [ 66 ]. Moreover, it was reported that peroxynitrite plays a role in triggering ischemic preconditioning and ischemic postconditioning [ 67 ].…”

Section: Discussionmentioning

confidence: 99%

Polyphenolic Compounds, Antioxidant, and Cardioprotective Effects of Pomace Extracts from Fetească Neagră Cultivar

Balea

Pârvu

Pop

et al. 2018

Oxidative Medicine and Cellular Longevity

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Grape pomace is a potential source of natural antioxidant agents. Phenolic compounds and antioxidant and cardioprotective properties of fresh and fermented pomace extracts obtained from Vitis vinifera L. red variety Fetească neagră grown in Romania in 2015 were investigated. Grape pomace extracts total phenolic index, total tannins, total anthocyanins, proanthocyanidins, flavan-3-ol monomers, stilbenes, and DPPH free radical scavenger were measured. The effect of a seven-day pretreatment with grape pomace extracts on the isoprenaline-induced infarct-like lesion in rats was assessed by ECG monitoring, serum levels of creatine kinase, aspartate transaminase, and alanine transaminase. Total serum oxidative status, total antioxidant response, oxidative stress index, malondialdehyde, total thiols, and nitric oxide have been also assessed. Higher phenolic content and antioxidant activity were found in fermented pomace extracts when compared to fresh pomace extracts. Pretreatment with grape pomace extracts significantly improved cardiac and oxidative stress parameters. In conclusion, Fetească neagră pomace extracts had a good in vitro antioxidant activity due to an important phenolic content. In vivo, the extracts had cardioprotective effects against isoprenaline-induced infarct-like lesion by reducing oxidative stress, fresh pomace extracts having a better effect.

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Section: Discussionmentioning

confidence: 99%

Polyphenolic Compounds, Antioxidant, and Cardioprotective Effects of Pomace Extracts from Fetească Neagră Cultivar

Balea

Pârvu

Pop

et al. 2018

Oxidative Medicine and Cellular Longevity

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“…To investigate gene expression changes at protein quantity and activity level, standard Western blot technique was used in case of phospho-AKT, AKT, phospho-FOXO3, and FOXO3 with GAPDH loading background at week 19 [Figure 1D; (38, 42, 43)]. Heart tissue samples ( n = 7–8) were homogenized with an ultrasonicator (UP100H Hielscher, Teltow, Germany) in RIPA (Radioimmunoassay) buffer (50 mM Tris–HCl (pH 8.0), 150 mM NaCl, 0.5% sodium deoxycholate, 5 mM EDTA, 0.1% SDS, 1% NP-40 (Cell Signaling, Carlsbad, CA, USA) supplemented with protease inhibitor cocktail and phosphatase inhibitors PMSF and NaF (Sigma, Saint Louis, MO, USA).…”

Section: Methodsmentioning

confidence: 99%

Selective Heart Irradiation Induces Cardiac Overexpression of the Pro-hypertrophic miR-212

et al. 2019

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Background: A deleterious, late-onset side effect of thoracic radiotherapy is the development of radiation-induced heart disease (RIHD). It covers a spectrum of cardiac pathology including also heart failure with preserved ejection fraction (HFpEF) characterized by left ventricular hypertrophy (LVH) and diastolic dysfunction. MicroRNA-212 (miR-212) is a crucial regulator of pathologic LVH via FOXO3-mediated pathways in pressure-overload-induced heart failure. We aimed to investigate whether miR-212 and its selected hypertrophy-associated targets play a role in the development of RIHD. Methods: RIHD was induced by selective heart irradiation (50 Gy) in a clinically relevant rat model. One, three, and nineteen weeks after selective heart irradiation, transthoracic echocardiography was performed to monitor cardiac morphology and function. Cardiomyocyte hypertrophy and fibrosis were assessed by histology at week 19. qRT-PCR was performed to measure the gene expression changes of miR-212 and forkhead box O3 (FOXO3) in all follow-up time points. The cardiac transcript level of other selected hypertrophy-associated targets of miR-212 including extracellular signal-regulated kinase 2 (ERK2), myocyte enhancer factor 2a (MEF2a), AMP-activated protein kinase, (AMPK), heat shock protein 40 (HSP40), sirtuin 1, (SIRT1), calcineurin A-alpha and phosphatase and tensin homolog (PTEN) were also measured at week 19. Cardiac expression of FOXO3 and phospho-FOXO3 were investigated at the protein level by Western blot at week 19. Results: In RIHD, diastolic dysfunction was present at every time point. Septal hypertrophy developed at week 3 and a marked LVH with interstitial fibrosis developed at week 19 in the irradiated hearts. In RIHD, cardiac miR-212 was overexpressed at week 3 and 19, and FOXO3 was repressed at the mRNA level only at week 19. In contrast, the total FOXO3 protein level failed to decrease in response to heart irradiation at week 19. Other selected hypertrophy-associated target genes failed to change at the mRNA level in RIHD at week 19. Conclusions: LVH in RIHD was associated with cardiac overexpression of miR-212. However, miR-212 seems to play a role in the development of LVH via FOXO3-independent mechanisms in RIHD. As a central regulator of pathologic remodeling, miR-212 might become a novel target for RIHD-induced LVH and heart failure.

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“…In parallel to the upregulation of NOX enzymes LPS increased the expression of eNOS and phosphor eNOS, which was accompanied by increased NO generation. Previous studies have demonstrated that injection of LPS into rats increased cardiac levels of the peroxynitrite precursors NO and superoxide which reacted towards peroxynitrite 38 . Enhanced peroxynitrite formation was previously detected in granulocytes, monocytes, lymphocytes and plasma cells after challenge with LPS 39 .…”

Section: Discussionmentioning

confidence: 88%

The pro‐inflammatory signature of lipopolysaccharide in spontaneous contracting embryoid bodies differentiated from mouse embryonic stem cells

Scharmacher,

Wartenberg,

Sauer

2023

J Cellular Molecular Medi

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Embryonic stem (ES) cells differentiate towards all three germ layers, including cardiac cells and leukocytes, and may be therefore suitable to model inflammatory reactions in vitro. In the present study, embryoid bodies differentiated from mouse ES cells were treated with increasing doses of lipopolysaccharide (LPS) to mimic infection with gram‐negative bacteria. LPS treatment dose‐dependent increased contraction frequency of cardiac cell areas and calcium spikes and increased protein expression of α‐actinin. LPS treatment increased the expression of the macrophage marker CD68 and CD69, which is upregulated after activation on T cells, B cells and NK cells. LPS dose‐dependent increased protein expression of toll‐like receptor 4 (TLR4). Moreover, upregulation of NLR family pyrin domain containing 3 (NLRP3), IL‐1ß and cleaved caspase 1 was observed, indicating activation of inflammasome. In parallel, generation of reactive oxygen species (ROS), nitric oxide (NO), and expression of NOX1, NOX2, NOX4 and eNOS occurred. ROS generation, NOX2 expression and NO generation were downregulated by the TLR4 receptor antagonist TAK‐242 which abolished the LPS‐induced positive chronotropic effect of LPS. In conclusion, our data demonstrate that LPS induced a pro‐inflammatory cellular immune response in tissues derived from ES cells, recommending the in vitro model of embryoid bodies for inflammation research.

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Low-Dose Endotoxin Induces Late Preconditioning, Increases Peroxynitrite Formation, and Activates STAT3 in the Rat Heart

Cited by 10 publications

References 54 publications

Polyphenolic Compounds, Antioxidant, and Cardioprotective Effects of Pomace Extracts from Fetească Neagră Cultivar

Polyphenolic Compounds, Antioxidant, and Cardioprotective Effects of Pomace Extracts from Fetească Neagră Cultivar

Selective Heart Irradiation Induces Cardiac Overexpression of the Pro-hypertrophic miR-212

The pro‐inflammatory signature of lipopolysaccharide in spontaneous contracting embryoid bodies differentiated from mouse embryonic stem cells

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