Reperfusion Injury in Patients With Acute Myocardial Infarction

Journal of the American College of Cardiology, Journal Year: 2024, Volume and Issue: 83(22), P. 2196 - 2213

Published: May 27, 2024

Language: Английский

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Endothelial Dysfunction: Redox Imbalance, NLRP3 Inflammasome, and Inflammatory Responses in Cardiovascular Diseases

Antioxidants, Journal Year: 2025, Volume and Issue: 14(3), P. 256 - 256

Published: Feb. 23, 2025

Endothelial dysfunction (ED) is characterized by an imbalance between vasodilatory and vasoconstrictive factors, leading to impaired vascular tone, thrombosis, inflammation. These processes are critical in the development of cardiovascular diseases (CVDs) such as atherosclerosis, hypertension ischemia/reperfusion injury (IRI). Reduced nitric oxide (NO) production increased oxidative stress key contributors ED. Aging further exacerbates ED through mitochondrial oxidative/nitrosative stress, heightening CVD risk. Antioxidant systems like superoxide-dismutase (SOD), glutathione-peroxidase (GPx), thioredoxin/thioredoxin-reductase (Trx/TXNRD) pathways protect against stress. However, their reduced activity promotes ED, vulnerability IRI. Metabolic syndrome, comprising insulin resistance, obesity, hypertension, often accompanied Specifically, hyperglycemia worsens endothelial damage promoting Obesity leads chronic inflammation changes perivascular adipose tissue, while associated with increase The NLRP3 inflammasome plays a significant role being triggered factors reactive oxygen nitrogen species, ischemia, high glucose, which contribute inflammation, injury, exacerbation Treatments, N-acetyl-L-cysteine, SGLT2 or inhibitors, show promise improving function. Yet complexity suggests that multi-targeted therapies addressing metabolic disturbances essential for managing CVDs syndrome.

Language: Английский

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Recent Progress and Prospects of Small Molecules for NLRP3 Inflammasome Inhibition

Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 66(21), P. 14447 - 14473

Published: Oct. 25, 2023

NLRP3 inflammasome is a multiprotein complex involved in host immune response─which exerts various biological effects by mediating the maturation and secretion of IL-1β IL-18─and pyroptosis. However, its aberrant activation could cause amplification inflammatory effects, thereby triggering range ailments, including Alzheimer's disease, Parkinson's rheumatoid arthritis, gout, type 2 diabetes mellitus, cancer. For past few years, as an attractive anti-inflammatory target, NLRP3-targeting small-molecule inhibitors have been widely reported both academic industrial communities. In order to deeply understand advancement inhibitors, we provide comprehensive insights commentary on drugs currently under clinical investigation, well other from chemical structure point view, with aim new for further development inflammasome-mediated diseases.

Language: Английский

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Inhibitors of NLRP3 Inflammasome in Ischemic Heart Disease: Focus on Functional and Redox Aspects

Antioxidants, Journal Year: 2023, Volume and Issue: 12(7), P. 1396 - 1396

Published: July 7, 2023

Myocardial ischemia-reperfusion injury (MIRI) is caused by several mechanisms, including the production of reactive oxygen species (ROS), altered cellular osmolarity, and inflammatory response. Calcium overload, levels, mitochondrial ROS are also involved in these MIRI processes, resulting irreversible opening permeability transition pore (mPTP). These mechanisms processes associated with NLRP3 inflammasome priming activation, which can induce cell death pyroptosis through up-regulation caspase-1 pathway IL-18 release. In addition, endothelial dysfunction, both presence absence MIRI, accompanied decreased nitric oxide production, overproduction, expression adhesion molecules leukocyte infiltration plays a central role, thus contributing, to alteration coronary flow, typical ischemic heart disease. Given intricate interrelationship between NLRP3, inhibitors reduce while oxidative stress inflammation. have been intensively studied as anti-inflammatory agents basic cardiovascular sciences. this review, we analyze interrelation disease effects some possible therapeutic condition. All compounds considered review need larger studies confirm their appropriate use clinical scenarios anti-ischemic drugs.

Language: Английский

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Acacetin inhibits inflammation by blocking MAPK/NF-κB pathways and NLRP3 inflammasome activation

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 8, 2024

Objective: Our preliminary research indicates that acacetin modulates the nucleotide-binding oligomerization domain (NOD)-like receptor pyrin containing 3 (NLRP3) inflammasome, providing protection against Alzheimer’s Disease (AD) and cerebral ischemic reperfusion injury. The mechanisms of to inhibit activation NLRP3 inflammasome remain fully elucidated. This study aims investigate effects potential on various agonists induced activation. Methods: A model for was established in mouse bone marrow-derived macrophages (BMDMs) using Monosodium Urate (MSU), Nigericin, Adenosine Triphosphate (ATP), Pam3CSK4, separately. Western blot analysis (WB) employed detect Pro-caspase-1, Pro-Interleukin-1β (Pro-IL-1β) cell lysates, caspase-1, IL-1β supernatants. Enzyme-Linked Immunosorbent Assay (ELISA) used measured release IL-1β, IL-18, Tumor Necrosis Factor-alpha (TNF-α) supernatants assess impact lactate dehydrogenase (LDH) also assessed. Nuclear Factor Kappa B (NF-κB) Mitogen-Activated Protein Kinase (MAPK) signaling pathways related proteins were evaluated by WB, NF-κB nuclear translocation observed via laser scanning confocal microscopy (LSCM). Disuccinimidyl Suberate (DSS) cross-linking Apoptosis-associated Speck-like protein a Caspase Recruitment Domain (ASC), LSCM observe Reactive Oxygen Species (ROS) production. Inductively Coupled Plasma (ICP) N-(6-methoxyquinolyl) acetoethyl ester (MQAE) assays utilized determined efflux potassium (K+) chloride (Cl-) ions. Results: Acacetin inhibited agonists, reducing TNF-α, LDH. It suppressed expression Lipopolysaccharides (LPS)-activated Phosphorylated ERK (p-ERK), p-JNK, p-p38, p65 phosphorylation translocation. reduced ROS production ASC aggregation, thus suppressing Notably, did not affect K+ Cl-ions during process. Conclusion: shows inhibitory both priming assembly processes positioning it as promising new candidate treatment inflammasome-related diseases.

Language: Английский

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Elucidating emerging signaling pathways driving endothelial dysfunction in cardiovascular aging

Vascular Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 107462 - 107462

Published: Jan. 1, 2025

Language: Английский

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The research progression of direct NLRP3 inhibitors to treat inflammatory disorders

Cellular Immunology, Journal Year: 2024, Volume and Issue: 397-398, P. 104810 - 104810

Published: Jan. 24, 2024

Language: Английский

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Novel NLRP3 inhibitor INF195: Low doses provide effective protection against myocardial ischemia/reperfusion injury

Vascular Pharmacology, Journal Year: 2024, Volume and Issue: 156, P. 107397 - 107397

Published: June 17, 2024

Several factors contribute to ischemia/reperfusion injury (IRI), including activation of the NLRP3 inflammasome and its byproducts, such as interleukin-1β (IL-1β) caspase-1. However, may paradoxically exhibit cardioprotective properties. This study aimed assess protective effects novel inhibitor, INF195, both in vitro ex vivo. To investigate relationship between myocardial IRI, we synthetized a series inhibitors, investigated their putative binding mode via docking studies. Through studies identified INF195 optimal for inhibition. We measured infarct-size isolated mouse hearts subjected 30-min global ischemia/one-hour reperfusion presence three different doses (5, 10, or 20-μM). analyzed caspase-1 IL-1β concentration cardiac tissue homogenates by ELISA. Statistical significance was determined using one-way ANOVA followed Tukey's test. reduces NLRP3-induced pyroptosis human macrophages. Heart pre-treatment with 5 10-μM significantly infarct size levels. Data suggest that intracardiac contributes IRI low exert reducing size. at 20-μM, efficacy declines, leading lack cardioprotection. Research is required determine if high have off-target dual roles, potentially eliminating harmful functions NLRP3. Our findings highlight potential new chemical scaffold, amenable further optimization, provide inhibition cardioprotection setting.

Language: Английский

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Immunotherapy targeting the obese white adipose tissue microenvironment: Focus on non-communicable diseases

Bioactive Materials, Journal Year: 2024, Volume and Issue: 35, P. 461 - 476

Published: Feb. 19, 2024

Obesity triggers inflammatory responses in the microenvironment of white adipose tissue, resulting chronic systemic inflammation and subsequent development non-communicable diseases, including type 2 diabetes, coronary heart disease, breast cancer. Current therapy approaches for obesity-induced diseases persist prioritizing symptom remission while frequently overlooking criticality targeting alleviating at its source. Accordingly, this review highlights importance obese tissue promising potential employing immunotherapy to target it as an effective therapeutic approach induced by obesity. Additionally, discusses challenges offers perspective about tissue.

Language: Английский

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Maresin 1 Attenuates Myocardium Ischemia/Reperfusion Injury via SIRT1/HMGB-1/NLRP-3-Related Mechanisms

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 177456 - 177456

Published: March 1, 2025

Language: Английский

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