Effect of TLR4/MyD88/NF‐kB axis in paraventricular nucleus on ventricular arrhythmias induced by sympathetic hyperexcitation in post‐myocardial infarction rats

Wang, Kang; You, Shuling; Hu, Hesheng; Li, Xiaolu; Yin, Jing; Shi, Yugen; Qı, Lei; Li, Pingjiang; Zhao, Yuepeng; Yan, Shi Fang

doi:10.1111/jcmm.17309

Cited by 21 publications

(11 citation statements)

References 44 publications

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“…Further, MSC-Exos post-treatment resulted in a pronounced reduction in TLR4 +ve cells (m–r), and MSC-Exos control alone (s–x) did not result in a significant increase in TLR4 expression. Furthermore, the nuclear/perinuclear localization of TLR4 observed in our study corroborates with previously published studies on TLR4 nuclear/perinuclear expression [ 9 , 30 , 31 ]. Additional quantitative analysis ( Figure 3 B) showed a significant ( p < 0.0001) increase in TLR4 +ve cells in the DOX group in comparison to the control along with a significant ( p < 0.0001) reduction in the DOX + MSC-Exos group.…”

Section: Resultssupporting

confidence: 93%

“…Previously published studies have shown that HMGB1, a DAMP, can activate various intracellular signaling pathways by interacting with TLR4 [ 14 , 28 , 29 ] hence we investigated nuclear/perinuclear TLR4 expression via ICC staining as previously published [ 9 , 30 , 31 ]. From the representative photomicrographs ( Figure 3 A), a noticeable increase in TLR4 +ve cells is observed in the DOX group (g–l) as compared to the control group (a–f).…”

Section: Resultsmentioning

confidence: 99%

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Mesenchymal Stem Cell-Derived Exosomes Ameliorate Doxorubicin-Induced Cardiotoxicity

Ali,

Singla

2024

Pharmaceuticals

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Doxorubicin (DOX) is an incessantly used chemotherapeutic drug that can cause detrimental dose-dependent effects such as cardiotoxicity and congestive heart failure. Hence, there is a need to discover innovative therapeutic approaches to counteract DOX-induced cardiotoxicity (DIC). MSC-Exos have shown to reduce apoptosis and cardiac fibrosis and promote cardiomyocyte proliferation in myocardial infracted mice. However, the effect of MSC-Exos on ameliorating DOX-induced pyroptosis has not been investigated. In this current study, H9c2 were first exposed to DOX to stimulate pyroptosis, followed by subsequent treatment with MSC-Exos, with further analysis performed through immunocytochemistry, western blotting, and RT-PCR. Our data depicted that post-treatment with MSC-Exos significantly (p < 0.05) reduced the HMGB1/TLR4 axis, inflammasome formation (NLRP3), pyroptotic markers (caspase-1, IL-1β, and IL-18), and the pyroptotic executioner (GSDMD) in DOX-treated H9c2 cells. In conclusion, our data show that MSC-Exos attenuates inflammation-induced pyroptosis in our in vitro DIC model. Our findings indicate that MSC-Exos may serve as a promising therapeutic intervention for mitigating DIC, as they maintain the therapeutic capabilities of MSCs while circumventing the drawbacks associated with traditional stem cell therapy.

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Section: Resultssupporting

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Mesenchymal Stem Cell-Derived Exosomes Ameliorate Doxorubicin-Induced Cardiotoxicity

Ali,

Singla

2024

Pharmaceuticals

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“…A low frequency (LF: 0.05-0.75 Hz) indicates parasympathetic and sympathetic tones, while a high frequency (HF: 0.75-2.5 Hz) indicates a parasympathetic tone. An LF/HF ratio increase indicated a cardiac sympathetic imbalance (34,35).…”

Section: Heart Rate Variability (Hrv) Measurementmentioning

confidence: 99%

lncRNA LOC100911717-targeting GAP43-mediated sympathetic remodeling after myocardial infarction in rats

Wang

Yin

et al. 2023

Front. Cardiovasc. Med.

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ObjectiveSympathetic remodeling after myocardial infarction (MI) is the primary cause of ventricular arrhythmias (VAs), leading to sudden cardiac death (SCD). M1-type macrophages are closely associated with inflammation and sympathetic remodeling after MI. Long noncoding RNAs (lncRNAs) are critical for the regulation of cardiovascular disease development. Therefore, this study aimed to identify the lncRNAs involved in MI and reveal a possible regulatory mechanism.Methods and resultsM0- and M1-type macrophages were selected for sequencing and screened for differentially expressed lncRNAs. The data revealed that lncRNA LOC100911717 was upregulated in M1-type macrophages but not in M0-type macrophages. In addition, the lncRNA LOC100911717 was upregulated in heart tissues after MI. Furthermore, an RNA pull-down assay revealed that lncRNA LOC100911717 could interact with growth-associated protein 43 (GAP43). Essentially, immunofluorescence assays and programmed electrical stimulation demonstrated that GAP43 expression was suppressed and VA incidence was reduced after lncRNA LOC100911717 knockdown in rat hearts using an adeno-associated virus.ConclusionsWe observed a novel relationship between lncRNA LOC100911717 and GAP43. After MI, lncRNA LOC100911717 was upregulated and GAP43 expression was enhanced, thus increasing the extent of sympathetic remodeling and the frequency of VA events. Consequently, silencing lncRNA LOC100911717 could reduce sympathetic remodeling and VAs.

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“…Malignant arrhythmia easily occurs after myocardial infarction, and its pathogenesis is associated with TLR4/NF-κBmediated inflammation and sympathetic hyperfunction, thus substantially decreasing the cardiac ejection function. However, after TLR4/NF-κB inhibition, the incidence of malignant arrhythmia after myocardial infarction significantly decreases [119,20]. Research has demonstrated that the main mechanisms through which TLR4/NF-κB aggravates myocardial infarction include inflammation [35], oxidative stress [120], and pyroptosis [70], and apoptosis [121].…”

Section: Myocardial Infarctionmentioning

confidence: 99%

Inappropriate Activation of TLR4/NF-κB is a Cause of Heart Failure

Zhou

Lin

et al. 2022

CVIA

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Significance: Heart failure, a disease with extremely high incidence, is closely associated with inflammation and oxidative stress. The Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) pathway plays an important role in the occurrence and development of heart failure. Recent advances: Previous studies have shown that TLR4/NF-κB causes heart failure by inducing oxidative stress and inflammation; damaging the endothelia; promoting fibrosis; and inducing myocardial hypertrophy, apoptosis, pyroptosis, and autophagy. Critical issues: Understanding the pathogenesis of heart failure is essential for the treatment of this disease. In this review, we outline the mechanisms underlying TLR4/NF-κB pathway-mediated heart failure and discuss drugs that alleviate heart failure by regulating the TLR4/NF-κB pathway. Future directions: During TLR4/NF-κB overactivation, interventions targeting specific receptor antagonists may effectively alleviate heart failure, thus providing a basis for the development of new anti-heart failure drugs.

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Effect of TLR4/MyD88/NF‐kB axis in paraventricular nucleus on ventricular arrhythmias induced by sympathetic hyperexcitation in post‐myocardial infarction rats

Cited by 21 publications

References 44 publications

Mesenchymal Stem Cell-Derived Exosomes Ameliorate Doxorubicin-Induced Cardiotoxicity

Mesenchymal Stem Cell-Derived Exosomes Ameliorate Doxorubicin-Induced Cardiotoxicity

lncRNA LOC100911717-targeting GAP43-mediated sympathetic remodeling after myocardial infarction in rats

Inappropriate Activation of TLR4/NF-κB is a Cause of Heart Failure

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