ROS-triggered endothelial cell death mechanisms: Focus on pyroptosis, parthanatos, and ferroptosis

Zheng, Duo; Liu, Jia; Piao, Hulin; Zhu, Zhicheng; Wei, Ran; Liu, Kexiang

doi:10.3389/fimmu.2022.1039241

Cited by 180 publications

(89 citation statements)

References 142 publications

(198 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…ROS has been found to play an important role in NLRP3 inflammasome activation [59][60][61]. Oxidative stress, as the upstream signal of NLRP3 inflammasome activation, can up-regulate the expression of NLRP3, procaspase-1, and ASC and promote the assembly of the NLRP3 inflammasome, which in turn causes pyroptosis [34]. Nrf-2 is an important redox transcription factor that can improve the oxidative stress status of the body and maintain the redox balance of cells by regulating the production of antioxidant enzymes [62].…”

Section: Discussionmentioning

confidence: 99%

“…As the activation of inflammasomes and release of inflammatory factors are important in the process of pyroptosis and the fact that oxidative stress can cause pyroptosis [34], we measured the levels of serum IL-1β, IL-18, SOD, GSH and MDA. The results showed that administration of DOX increased the serum levels of IL-1β, IL-18, MDA and decreased the serum levels of SOD and GSH compared to that in the control group, while AS-IV treatment decreased serum IL-1β, IL-18, MDA and increased SOD and GSH levels (Fig.…”

Section: As-iv Attenuates Dox-induced Inflammation and Oxidative Stressmentioning

confidence: 99%

See 1 more Smart Citation

Astragaloside IV Inhibits NLRP3 Inflammasome-Mediated Pyroptosis via Activation of Nrf-2/HO-1 Signaling Pathway and Protects against Doxorubicin-Induced Cardiac Dysfunction

Chen¹,

Tian²,

Zhang³

et al. 2023

Front. Biosci. (Landmark Ed)

View full text Add to dashboard Cite

Background: Doxorubicin (DOX) is an effective broad-spectrum antitumor drug, but its clinical application is limited due to the side effects of cardiac damage. Astragaloside IV (AS-IV) is a significant active component of Astragalus membranaceus that exerts cardioprotective effects through various pathways. However, whether AS-IV exerts protective effects against DOX-induced myocardial injury by regulating the pyroptosis is still unknown and is investigated in this study. Methods: The myocardial injury model was constructed by intraperitoneal injection of DOX, and AS-IV was administered via oral gavage to explore its specific protective mechanism. Cardiac function and cardiac injury indicators, including lactate dehydrogenase (LDH), cardiac troponin I (cTnI), creatine kinase isoenzyme (CK-MB), and brain natriuretic peptide (BNP), and histopathology of the cardiomyocytes were assessed 4 weeks post DOX challenge. Serum levels of IL-1β, IL-18, superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) and the expression of pyroptosis and signaling proteins were also determined. Results: Cardiac dysfunction was observed after the DOX challenge, as evidenced by reduced ejection fraction, increased myocardial fibrosis, and increased BNP, LDH, cTnI, and CK-MB levels (p < 0.05, N = 3-10). AS-IV attenuated DOX-induced myocardial injury. The mitochondrial morphology and structure were also significantly damaged after DOX treatment, and these changes were restored after AS-IV treatment. DOX induced an increase in the serum levels of IL-1β, IL-18, SOD, MDA and GSH as well as an increase in the expression of pyroptosis-related proteins (p < 0.05, N = 3-6). Besides, AS-IV depressed myocardial inflammatory-related pyroptosis via activation of the expressions of nuclear factor E2-related factor 2 (Nrf-2) and heme oxygenase 1 (HO-1) (p < 0.05, N = 3). Conclusions: Our results showed that AS-IV had a significant protective effect against DOX-induced myocardial injury, which may be associated with the activation of Nrf-2/HO-1 to inhibit pyroptosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: As-iv Attenuates Dox-induced Inflammation and Oxidative Stressmentioning

confidence: 99%

Astragaloside IV Inhibits NLRP3 Inflammasome-Mediated Pyroptosis via Activation of Nrf-2/HO-1 Signaling Pathway and Protects against Doxorubicin-Induced Cardiac Dysfunction

Chen¹,

Tian²,

Zhang³

et al. 2023

Front. Biosci. (Landmark Ed)

View full text Add to dashboard Cite

show abstract

“…miR-30c decreases the production of reactive oxygen species (ROS) ( 51 , 52 ), which are key for tissue damage and myocardial protection. Furthermore, it is widely reported that overactivation of ROS pathway signaling increases pyroptosis ( 53 , 54 ). During MI/R injury, excessive production ROS and increased pyroptosis of cardiomyocytes may be induced by decreased expression of miR-30c.…”

Section: Discussionmentioning

confidence: 99%

miR‑30c reduces myocardial ischemia/reperfusion injury by targeting SOX9 and suppressing pyroptosis

Nie

Zhou

et al. 2023

Exp Ther Med

View full text Add to dashboard Cite

MicroRNAs (miRNAs or miRs) are commonly involved in regulating myocardial ischemia/reperfusion (I/R) injury by binding and silencing their target genes. However, whether miRNAs regulate myocardial I/R-induced pyroptosis remains unclear. The present study established an in vivo rat model of myocardial I/R injury and in vitro hypoxia/reoxygenation (H/R) injury model in rat primary cardiomyocytes to investigate the function and the underlying mechanisms of miRNAs on I/R injury-induced pyroptosis. RNA sequencing was utilized to select the candidate miRNAs between normal and I/R group. Reverse transcription-quantitative PCR and western blotting were performed to detect candidate miRNAs (miR-30c-5p, also known as miR-30c) and SRY-related high mobility group-box gene 9 (SOX9) expression, as well as expression of pyroptosis-associated proteins (NF-κB, ASC, caspase-1, NLRP3) in the myocardial I/R model. ELISA was used to measure pyroptosis-associated inflammatory markers IL-18 and IL-1β. Moreover, the link between miR-30c and SOX9 was predicted using bioinformatics and luciferase reporter assay. In myocardial I/R injured rats, miR-30c was downregulated, while the expression of SOX9 was upregulated. Overexpression of miR-30c inhibited pyroptosis both in vivo and in vitro . Furthermore, miR-30c negatively regulated SOX9 expression by binding its 3'untranslated region. In conclusion, the miR-30c/SOX9 axis decreased myocardial I/R injury by suppressing pyroptosis, which may be a potential therapeutic target.

show abstract

“…Hydrogen peroxide, superoxide anions, and hydroxyl radicals are the sources of the intracellular ROS production [ 80 ]. Zheng et al [ 81 ] systematically reviewed the sources of endothelial ROS production and their underlying mechanism on ECs death. Moreover, ROS also increases intracellular calcium concentration and activates proto-oncogenes and pro-inflammatory genes [ 82 ].…”

Section: Hydroxytyrosol In Oxidative Stress-induced Endothelial Dysfu...mentioning

confidence: 99%

Effects of Hydroxytyrosol in Endothelial Functioning: A Comprehensive Review

et al. 2023

View full text Add to dashboard Cite

Pharmacologists have been emphasizing and applying plant and herbal-based treatments in vascular diseases for decades now. Olives, for example, are a traditional symbol of the Mediterranean diet. Hydroxytyrosol is an olive-derived compound known for its antioxidant and cardioprotective effects. Acknowledging the merit of antioxidants in maintaining endothelial function warrants the application of hydroxytyrosol in endothelial dysfunction salvage and recovery. Endothelial dysfunction (ED) is an impairment of endothelial cells that adversely affects vascular homeostasis. Disturbance in endothelial functioning is a known precursor for atherosclerosis and, subsequently, coronary and peripheral artery disease. However, the effects of hydroxytyrosol on endothelial functioning were not extensively studied, limiting its value either as a nutraceutical supplement or in clinical trials. The action of hydroxytyrosol in endothelial functioning at a cellular and molecular level is gathered and summarized in this review. The favorable effects of hydroxytyrosol in the improvement of endothelial functioning from in vitro and in vivo studies were scrutinized. We conclude that hydroxytyrosol is capable to counteract oxidative stress, inflammation, vascular aging, and arterial stiffness; thus, it is beneficial to preserve endothelial function both in vitro and in vivo. Although not specifically for endothelial dysfunction, hydroxytyrosol safety and efficacy had been demonstrated via in vivo and clinical trials for cardiovascular-related studies.

show abstract

ROS-triggered endothelial cell death mechanisms: Focus on pyroptosis, parthanatos, and ferroptosis

Cited by 180 publications

References 142 publications

Astragaloside IV Inhibits NLRP3 Inflammasome-Mediated Pyroptosis via Activation of Nrf-2/HO-1 Signaling Pathway and Protects against Doxorubicin-Induced Cardiac Dysfunction

Astragaloside IV Inhibits NLRP3 Inflammasome-Mediated Pyroptosis via Activation of Nrf-2/HO-1 Signaling Pathway and Protects against Doxorubicin-Induced Cardiac Dysfunction

miR‑30c reduces myocardial ischemia/reperfusion injury by targeting SOX9 and suppressing pyroptosis

Effects of Hydroxytyrosol in Endothelial Functioning: A Comprehensive Review

Contact Info

Product

Resources

About