Role of pyroptosis in cardiovascular disease

Cell Proliferation, Journal Year: 2018, Volume and Issue: 52(2)

Published: Dec. 7, 2018

Abstract Cardiac function is determined by the dynamic equilibrium of various cell types and extracellular matrix that composes heart. Cardiovascular diseases (CVDs), especially atherosclerosis myocardial infarction, are often accompanied death acute/chronic inflammatory reactions. Caspase‐dependent pyroptosis characterized activation pathways leading to NOD‐like receptors, NLRP3 inflammasome its downstream effector factors interleukin (IL)‐1β IL‐18. Many studies in past decade have investigated role CVDs. The findings these led development therapeutic approaches based on regulation pyroptosis, some clinical trials. This review summarizes molecular mechanisms, cellular effects briefly then discusses current CVD research.

Language: Английский

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NLRP3 inflammasome in endothelial dysfunction

Cell Death and Disease, Journal Year: 2020, Volume and Issue: 11(9)

Published: Sept. 18, 2020

Abstract Inflammasomes are a class of cytosolic protein complexes. They act as innate immune signal receptors to sense pathogens and initiate inflammatory responses under physiological pathological conditions. The NLR-family pyrin domain-containing 3 (NLRP3) inflammasome is the most characteristic multimeric complex. Its activation triggers cleavage pro-interleukin (IL)-1β pro-IL-18, which mediated by caspase-1, secretes mature forms these mediators from cells promote further process oxidative stress. Simultaneously, undergo pro-inflammatory programmed cell death, termed pyroptosis. danger signals for activating NLRP3 very extensive, especially reactive oxygen species (ROS), an intermediate trigger activate inflammasome, exacerbating subsequent cascades damage. Vascular endothelium at site inflammation actively involved in regulation progression with important implications cardiovascular homeostasis dynamically adaptable interface. Endothelial dysfunction hallmark predictor ailments or adverse events, such coronary artery disease, diabetes mellitus, hypertension, hypercholesterolemia. loss proper endothelial function may lead tissue swelling, chronic inflammation, formation thrombi. As such, elimination clinical relevance. In this review, we provided comprehensive perspective on pivotal role aggravating stress possible underlying mechanisms. Furthermore, highlighted contribution noncoding RNAs activation-associated dysfunction, outlined potential drugs targeting dysfunction. Collectively, summary provides recent developments perspectives how interferes research value mediator

Language: Английский

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Pyroptosis in inflammatory diseases and cancer

Theranostics, Journal Year: 2022, Volume and Issue: 12(9), P. 4310 - 4329

Published: Jan. 1, 2022

Pyroptosis is a lytic and inflammatory type of programmed cell death that usually triggered by inflammasomes executed gasdermin proteins. The main characteristics pyroptosis are swelling, membrane perforation, the release contents. In normal physiology, plays critical role in host defense against pathogen infection. However, excessive may cause immoderate continuous responses involves occurrence diseases. Attractively, as immunogenic death, can serve new strategy for cancer elimination inducing pyroptotic activating intensely antitumor immunity. To make good use this double-edged sword, molecular mechanisms, therapeutic implications related diseases need to be fully elucidated. review, we first systematically summarize signaling pathways then present available evidences indicating cancer. Based on this, focus recent progress strategies inhibit treatment diseases, those induce therapy. Overall, should shed light future directions provide novel ideas using powerful tool fight

Language: Английский

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Melatonin prevents Drp1‐mediated mitochondrial fission in diabetic hearts through SIRT1‐PGC1α pathway

Journal of Pineal Research, Journal Year: 2018, Volume and Issue: 65(2)

Published: March 25, 2018

Abstract Myocardial contractile dysfunction is associated with an increase in mitochondrial fission patients diabetes. However, whether directly promotes diabetes‐induced cardiac still unknown. Melatonin exerts a substantial influence on the regulation of fission/fusion. This study investigated melatonin protects against via fission/fusion and explored its underlying mechanisms. Here, we show that prevented by inhibiting dynamin‐related protein 1 (Drp1)‐mediated fission. treatment decreased Drp1 expression, inhibited fragmentation, suppressed oxidative stress, reduced cardiomyocyte apoptosis, improved function streptozotocin ( STZ )‐induced diabetic mice, but not SIRT −/− mice. In high glucose‐exposed H9c2 cells, increased expression PGC ‐1α Drp1‐mediated mitochondria‐derived superoxide production. contrast, or si RNA knockdown blunted inhibitory effects These data indicated exerted cardioprotective reducing 1/ ‐1α‐dependent manner. Moreover, chromatin immunoprecipitation analysis revealed regulated binding to promoter. Inhibition inhibitor mdivi‐1 alleviated findings attenuates development preventing through 1‐ 1α pathway, which negatively regulates directly. may be potential target for delaying complications

Language: Английский

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Aging, Melatonin, and the Pro- and Anti-Inflammatory Networks

International Journal of Molecular Sciences, Journal Year: 2019, Volume and Issue: 20(5), P. 1223 - 1223

Published: March 11, 2019

Aging and various age-related diseases are associated with reductions in melatonin secretion, proinflammatory changes the immune system, a deteriorating circadian sirtuin-1 (SIRT1) activity. In non-tumor cells, several effects of abolished by inhibiting SIRT1, indicating mediation SIRT1. Melatonin is, addition to its antioxidant roles, an stimulatory agent. However, it can act as either pro- or anti-inflammatory regulator context-dependent way. stimulate release cytokines other mediators, but also, under different conditions, suppress inflammation-promoting processes such NO release, activation cyclooxygenase-2, inflammasome NLRP3, gasdermin D, toll-like receptor-4 mTOR signaling, cytokine SASP (senescence-associated secretory phenotype), amyloid-β toxicity. It also activates network, which SIRT1 activation, upregulation Nrf2 downregulation NF-κB, IL-4 IL-10 involved. A perhaps crucial action may be promotion macrophage microglia polarization favor phenotype M2. addition, many factors networks subject regulation microRNAs that target mRNAs respective upregulate them targeting their inhibitor proteins.

Language: Английский

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Endothelial cell pyroptosis plays an important role in Kawasaki disease via HMGB1/RAGE/cathespin B signaling pathway and NLRP3 inflammasome activation

Cell Death and Disease, Journal Year: 2019, Volume and Issue: 10(10)

Published: Oct. 14, 2019

Abstract Kawasaki disease (KD) is the most common cause of pediatric cardiac in developed countries, and can lead to permanent coronary artery damage long term sequelae such as aneurysms. Given prevalence severity KD, further research warranted on its pathophysiology. It known that endothelial cell inflammation are two essential processes resulting dysfunction KD. However, detailed mechanisms largely unknown. In this study, we investigated role pyroptosis setting hypothesized may play a central vivo experiments patients with KD demonstrated serum levels pyroptosis-related proteins, including ASC, caspase-1, IL-1β, IL-18, GSDMD lactic dehydrogenase (LDH), were significantly increased compared healthy controls (HCs). Moreover, western blot analysis showed expression mature IL-1β was notably elevated sera. vitro, exposure human umbilical vein cells (HUVECs) sera-treated THP1 resulted activation NLRP3 inflammasome subsequent induction, evidenced by GSDMD, cleaved p30 form LDH release TUNEL propidium iodide (PI)-positive cells. Furthermore, our results NLRP3-dependent activated HMGB1/RAGE/cathepsin B signaling. These findings also recapitulated mouse model induced Candida albicans wall extracts (CAWS). Together, suggest significant providing novel evidence elucidates

Language: Английский

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Protective role of melatonin in cardiac ischemia‐reperfusion injury: From pathogenesis to targeted therapy

Journal of Pineal Research, Journal Year: 2018, Volume and Issue: 64(3)

Published: Jan. 24, 2018

Abstract Acute myocardial infarction ( MI ) is a major cause of mortality and disability worldwide. In patients with , the treatment option for reducing acute ischemic injury limiting size timely effective reperfusion using either thombolytic therapy or primary percutaneous coronary intervention PCI ). However, procedure itself induces cardiomyocyte death, known as injury, which there still no therapy. Recent evidence has depicted promising role melatonin, possesses powerful antioxidative anti‐inflammatory properties, in prevention ischemia‐reperfusion IR protection against death. A number reports explored mechanism action behind melatonin‐induced beneficial effects injury. this review, we summarize research progress related to discuss unique actions melatonin protective agent. Furthermore, possible mechanisms responsible benefits are listed prospect use clinical application.

Language: Английский

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Role of pyroptosis in cardiovascular diseases

International Immunopharmacology, Journal Year: 2018, Volume and Issue: 67, P. 311 - 318

Published: Dec. 17, 2018

Language: Английский

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Cisplatin Induces Pyroptosis via Activation of MEG3/NLRP3/caspase-1/GSDMD Pathway in Triple-Negative Breast Cancer

International Journal of Biological Sciences, Journal Year: 2021, Volume and Issue: 17(10), P. 2606 - 2621

Published: Jan. 1, 2021

Cisplatin (DDP) was reported to improve pathological complete response (pCR) rates in triple-negative breast cancer (TNBC) patients, however, the molecular mechanism still remains largely unknown.Emerging evidence suggested that some chemotherapeutic drugs played anti-tumor effects by inducing cell pyroptosis.Nevertheless, whether pyroptosis contributes DDP-induced effect TNBC unexploited.In present study, NLRP3/caspase-1/GSDMD pathway involved of vitro and vivo, providing DDP might induce TNBC.Moreover, activated up-regulating long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3).Furthermore, knockdown MEG3 not only partly abolished activation on pathway-mediated pyroptosis, but also reversed suppression tumor growth metastasis ability further confirming may partially mediate pyroptotic signaling upon treatment.Thus, our data uncovered a novel induced via MEG3/NLRP3/caspase-1/GSDMD exert effects, which help develop new strategies for therapeutic interventions TNBC.

Language: Английский

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Role of Lipid Accumulation and Inflammation in Atherosclerosis: Focus on Molecular and Cellular Mechanisms

Frontiers in Cardiovascular Medicine, Journal Year: 2021, Volume and Issue: 8

Published: Sept. 6, 2021

Atherosclerosis is a chronic lipid-driven and maladaptive inflammatory disease of arterial intima. It characterized by the dysfunction lipid homeostasis signaling pathways that control inflammation. This article reviews role inflammation accumulation, especially low-density lipoprotein (LDL), in pathogenesis atherosclerosis, with more emphasis on cellular mechanisms. Furthermore, this review will briefly highlight medicinal plants, long non-coding RNA (lncRNA), microRNAs pathophysiology, treatment, prevention atherosclerosis. Lipid at various levels, including receptor-mediated uptake, synthesis, storage, metabolism, efflux, its impairments are important for development The major source cholesterol accumulation wall proatherogenic modified (mLDL). Modified lipoproteins, such as oxidized (ox-LDL) LDL binding proteoglycans extracellular matrix intima blood vessels, cause aggregation particles, endothelial damage, leukocyte recruitment, foam cell formation, Inflammation key contributor to atherosclerosis participates all phases Also, several studies have shown lncRNAs appeared regulators physiological pathophysiological processes regulation HDL biogenesis, regulating smooth muscle proliferation, controlling Thus, both immune response closely linked, their molecular interact each other.

Language: Английский

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