Angelica sinensis Polysaccharide Suppresses Pyroptosis in Myocardial Ischemia/Reperfusion Injury via the FN1/NF-κB/NLRP3 Pathway DOI Creative Commons
Xiaowei Niu, Wenjun Zhang, Fei Zhao

и другие.

Natural Product Communications, Год журнала: 2024, Номер 19(9)

Опубликована: Сен. 1, 2024

Background Pyroptosis, a form of inflammatory programmed cell death, has recently emerged as pivotal factor in the pathogenesis myocardial ischemia/reperfusion (MI/R) injury. Despite its significance, effective therapeutic strategies targeting MI/R-induced pyroptosis remain elusive current clinical practice. Previous studies have demonstrated promising anti-inflammatory effects Angelica sinensis polysaccharide (ASP) context certain disorders. Objectives We aimed to investigate ASP on MI/R injury and elucidate potential molecular mechanisms by combining transcriptomic analysis with complementary vivo vitro experiments. Materials methods H9c2 cells were used establish hypoxia/reoxygenation (H/R) model, was induced rats ligating releasing left anterior coronary artery. Myocardial tissue samples harvested for sequencing bioinformatic analyses. Cardioprotective evaluated through electrocardiography, echocardiography, histological examination. Enzyme-linked immunosorbent assay (ELISA) employed quantify levels mediators. Biochemical assays conducted assess biomarkers Caspase-1 activity. Western blotting performed analyze protein expression Fibronectin 1 (FN1), Nuclear kappa B (NF-κB) p65, phosphorylated NF-κB p65 (p-NF-κB p65), Nod-like receptor 3 (NLRP3), Gasdermin-D (GSDMD). Results Pretreatment conferred potent cardioprotective rat model injury, evidenced significant attenuation infarct size, enzyme levels, ST-segment elevation alongside notable improvements cardiac function. Transcriptomic profiling unveiled that differentially expressed genes modulated treatment predominantly implicated pyroptosis-elicited response. Concordantly, both experiments substantiated effectively attenuated pyroptosis, manifested diminished pyroptosis-related indicators, encompassing proportion TUNEL-positive cells, activation, GSDMD cleavage, liberation pro-inflammatory cytokines. Further mechanistic investigations revealed inhibition FN1/NF-κB/NLRP3 signaling pathway. Conclusions Our investigation, leveraging system-level profiling, demonstrates confers against suppression cardiomyocyte culminating from downregulation

Язык: Английский

Aerobic exercise mitigates high-fat diet-induced cardiac dysfunction, pyroptosis, and inflammation by inhibiting STING-NLRP3 signaling pathway DOI

Zujie Xu,

Zheying Ma,

Xiaoqin Zhao

и другие.

Molecular and Cellular Biochemistry, Год журнала: 2024, Номер 479(12), С. 3459 - 3470

Опубликована: Фев. 22, 2024

Язык: Английский

Процитировано

4
The redox-active defensive Selenoprotein T as a novel stress sensor protein playing a key role in the pathophysiology of heart failure DOI Creative Commons

Anna De Bartolo,

Teresa Pasqua,

Naomi Romeo

и другие.

Journal of Translational Medicine, Год журнала: 2024, Номер 22(1)

Опубликована: Апрель 20, 2024

Abstract Maladaptive cardiac hypertrophy contributes to the development of heart failure (HF). The oxidoreductase Selenoprotein T (SELENOT) emerged as a key regulator during rat cardiogenesis and acute protection. However, its action in chronic settings dysfunction is not understood. Here, we investigated role SELENOT pathophysiology HF: (i) by designing small peptide (PSELT), recapitulating activity via redox site, assessed beneficial preclinical model HF [aged spontaneously hypertensive (SHHF) rats] against isoproterenol (ISO)-induced ventricular H9c2 adult human AC16 cardiomyocytes; (ii) evaluating intra-cardiomyocyte production secretion under hypertrophied stimulation. Results showed that PSELT attenuated systemic inflammation, lipopolysaccharide (LPS)-induced macrophage M1 polarization, myocardial injury, severe ultrastructural alterations, while counteracting mediators fibrosis, aging, DNA damage restoring desmin downregulation upregulation failing hearts. In hemodynamic assessment, improved contractile impairment at baseline following ischemia/reperfusion reduced infarct size normal At cellular level, counteracted ISO-mediated alterations through motif, mitigating ISO-triggered intracellular secretion, phenomenon presumably reflects extent cell damage. Altogether, these results indicate could represent novel sensor cardiomyocytes potential PSELT-based new therapeutic approach HF. Graphical

Язык: Английский

Процитировано

3
Inhibitors of NLRP3 Inflammasome Formation: A Cardioprotective Role for the Gasotransmitters Carbon Monoxide, Nitric Oxide, and Hydrogen Sulphide in Acute Myocardial Infarction DOI Open Access
Fergus M. Payne,

Alisha R. Dabb,

Joanne C. Harrison

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(17), С. 9247 - 9247

Опубликована: Авг. 26, 2024

Myocardial ischaemia reperfusion injury (IRI) occurring from acute coronary artery disease or cardiac surgical interventions such as bypass surgery can result in myocardial dysfunction, presenting as, “stunning”, arrhythmias, infarction, and adverse remodelling, may lead to both a systemic localised inflammatory response. This response is regulated through the nucleotide-binding oligomerisation domain (NACHT), leucine-rich repeat (LRR)-containing protein family pyrin (PYD)-3 (NLRP3) inflammasome, multimeric structure whose components are present within cardiomyocytes fibroblasts. The NLRP3 inflammasome activated via numerous danger signals produced by IRI central resultant innate immune Inhibition of this inherent has been shown protect myocardium stop occurrence syndrome following re-establishment circulation. Therapies prevent formation clinic currently lacking, therefore, new pharmacotherapies required. review will highlight role during examine therapeutic value inhibition with particular attention carbon monoxide, nitric oxide, hydrogen sulphide potential pharmacological inhibitors activation.

Язык: Английский

Процитировано

2
Benidipine Hydrochloride Inhibits NLRP3 Inflammasome Activation by Inhibiting LPS-Induced NF-κB Signaling in THP-1 Macrophages DOI Creative Commons

Mengmeng Huo,

Wanying Guo, Liqiong Ding

и другие.

Journal of Inflammation Research, Год журнала: 2024, Номер Volume 17, С. 6307 - 6316

Опубликована: Сен. 1, 2024

NLRP3, ASC, and procaspase-1 form the multiprotein complex known as NLRP3 inflammasome. Following priming of by TLR4 ligand, activation inflammasome causes caspase-1 maturation, which results in release IL-1β. Calcium channel antagonists are commonly employed antihypertensive medications have anti-inflammatory properties through inhibition cytokine release, specifically The impact calcium on inflammasomes, however, has not been well studied. This study aimed to investigate effect blocker benidipine hydrochloride LPS-induced THP-1 macrophages its possible mechanism.

Язык: Английский

Процитировано

1
Design, synthesis and biological evaluation of sulfonylurea derivatives as NLRP3 inflammasome inhibitors DOI
Haonan Feng, Donglai Li,

Fuli Zhu

и другие.

Bioorganic & Medicinal Chemistry Letters, Год журнала: 2024, Номер 114, С. 129987 - 129987

Опубликована: Окт. 11, 2024

Язык: Английский

Процитировано

1
A recombinant fragment antigen-binding (Fab) of trastuzumab displays low cytotoxic profile in adult human cardiomyocytes: first evidence and the key implication of FcγRIIA receptor DOI

Anna De Bartolo,

Naomi Romeo,

Alessandro Marrone

и другие.

Acta Pharmacologica Sinica, Год журнала: 2024, Номер unknown

Опубликована: Окт. 16, 2024

Язык: Английский

Процитировано

1
Role of dietary inflammatory index in the association of NT-proBNP with all-cause and cardiovascular mortality in NHANES 1999–2004 DOI Creative Commons
Lihua Xie, Jia Liu,

Xiaochi Wang

и другие.

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Авг. 28, 2024

N-terminal pro-Brain-type natriuretic peptide (NT-proBNP) has a predictive value of cardiovascular disease (CVD). Pro-inflammatory diet been proven to be related CVD. Our study investigated whether the association between NT-proBNP and mortality differed among general U.S. adults with different dietary inflammatory index (DII) scores. This utilized National Health Nutrition Examination Surveys (NHANES) database from 1999 2004. Non-pregnant aged ≥ 20 years without CVD were included. Cox regression model restricted cubic splines used investigate associations NT-proBNP, DII, mortality. A total 9788 included, 2386 all-cause deaths 668 occurred over 17.08 follow-up. was positively associated DII scores (P < 0.001). Among subjects CVD, elevated an increased risk mortality, per unit increase in log transformed by approximately 1.40 times (HR 2.397, 95%CI 1.966-2.922, P 0.001) 2.89 3.889, 2.756-5.490, after adjusting for factors, similar results observed Besides, significant interaction found lgNT-proBNP on (all 0.05). While as quartiles increased, partially weakened. findings reveal that pro-inflammatory may explain warrant further study.

Язык: Английский

Процитировано

0
Angelica sinensis Polysaccharide Suppresses Pyroptosis in Myocardial Ischemia/Reperfusion Injury via the FN1/NF-κB/NLRP3 Pathway DOI Creative Commons
Xiaowei Niu, Wenjun Zhang, Fei Zhao

и другие.

Natural Product Communications, Год журнала: 2024, Номер 19(9)

Опубликована: Сен. 1, 2024

Background Pyroptosis, a form of inflammatory programmed cell death, has recently emerged as pivotal factor in the pathogenesis myocardial ischemia/reperfusion (MI/R) injury. Despite its significance, effective therapeutic strategies targeting MI/R-induced pyroptosis remain elusive current clinical practice. Previous studies have demonstrated promising anti-inflammatory effects Angelica sinensis polysaccharide (ASP) context certain disorders. Objectives We aimed to investigate ASP on MI/R injury and elucidate potential molecular mechanisms by combining transcriptomic analysis with complementary vivo vitro experiments. Materials methods H9c2 cells were used establish hypoxia/reoxygenation (H/R) model, was induced rats ligating releasing left anterior coronary artery. Myocardial tissue samples harvested for sequencing bioinformatic analyses. Cardioprotective evaluated through electrocardiography, echocardiography, histological examination. Enzyme-linked immunosorbent assay (ELISA) employed quantify levels mediators. Biochemical assays conducted assess biomarkers Caspase-1 activity. Western blotting performed analyze protein expression Fibronectin 1 (FN1), Nuclear kappa B (NF-κB) p65, phosphorylated NF-κB p65 (p-NF-κB p65), Nod-like receptor 3 (NLRP3), Gasdermin-D (GSDMD). Results Pretreatment conferred potent cardioprotective rat model injury, evidenced significant attenuation infarct size, enzyme levels, ST-segment elevation alongside notable improvements cardiac function. Transcriptomic profiling unveiled that differentially expressed genes modulated treatment predominantly implicated pyroptosis-elicited response. Concordantly, both experiments substantiated effectively attenuated pyroptosis, manifested diminished pyroptosis-related indicators, encompassing proportion TUNEL-positive cells, activation, GSDMD cleavage, liberation pro-inflammatory cytokines. Further mechanistic investigations revealed inhibition FN1/NF-κB/NLRP3 signaling pathway. Conclusions Our investigation, leveraging system-level profiling, demonstrates confers against suppression cardiomyocyte culminating from downregulation

Язык: Английский

Процитировано

0