NLRP3 inflammasome and interleukin-1 contributions to COVID-19-associated coagulopathy and immunothrombosis

Cardiovascular Research, Год журнала: 2023, Номер 119(11), С. 2046 - 2060

Опубликована: Май 30, 2023

Abstract Immunothrombosis—immune-mediated activation of coagulation—is protective against pathogens, but excessive immunothrombosis can result in pathological thrombosis and multiorgan damage, as severe coronavirus disease 2019 (COVID-19). The NACHT-, LRR-, pyrin domain-containing protein 3 (NLRP3) inflammasome produces major proinflammatory cytokines the interleukin (IL)-1 family, IL-1β IL-18, induces pyroptotic cell death. Activation NLRP3 pathway also promotes immunothrombotic programs including release neutrophil extracellular traps tissue factor by leukocytes, prothrombotic responses platelets vascular endothelium. occurs patients with COVID-19 pneumonia. In preclinical models, blockade restrains COVID-19-like hyperinflammation pathology. Anakinra, recombinant human IL-1 receptor antagonist, showed safety efficacy is approved for treatment hypoxaemic early signs hyperinflammation. non-selective inhibitor colchicine reduced hospitalization death a subgroup outpatients not COVID-19. Additional trials testing blockers are inconclusive or ongoing. We herein outline contribution to COVID-19-associated coagulopathy, review clinical evidence suggesting an engagement pathogenesis summarize current efforts target COVID-19, discuss challenges, unmet gaps, therapeutic potential that inflammasome-targeted strategies may provide inflammation-driven thrombotic disorders

Язык: Английский

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Insights into Cancer-Associated Thrombosis Leading Towards Ischemic Stroke

Biology, Год журнала: 2025, Номер 14(1), С. 50 - 50

Опубликована: Янв. 10, 2025

Stroke leads to significant disability in most patients, whereas cancer elevates the occurrence of stroke. The incidence cancer-associated stroke (CAS) is projected rise as a result improvements therapies. Various forms have been demonstrated be linked ischemic Cancer might influence pathophysiology either directly or through coagulation that creates hypercoagulative state, addition infections. Treatment methods for cancer, including chemotherapy, radiotherapy, and surgery, all increase risk well. This review discusses subtypes, epidemiology, pathophysiology, mechanisms within biomarkers, signaling pathways while providing vital information on involved transcription factors, treatment, management patients with Atherosclerosis, extracellular vesicles (EVs), biomolecules can also affect CAS. Overall, not uncommon complication there an immediate demand neurologists oncologists create strategies screening preventing strokes patients.

Язык: Английский

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Old and New Biomarkers in Idiopathic Recurrent Acute Pericarditis (IRAP): Prognosis and Outcomes

Current Cardiology Reports, Год журнала: 2025, Номер 27(1)

Опубликована: Янв. 11, 2025

Abstract Purpose of Review To outline the latest discoveries regarding utility and reliability serum biomarkers in idiopathic recurrent acute pericarditis (IRAP), considering recent findings on its pathogenesis. The study highlights predictive role these potential short- (cardiac tamponade, recurrences) long-term complications (constrictive pericarditis, death). Recent Findings pathogenesis has been better defined years, focusing autoinflammatory pathway. New studies have demonstrated pivotal classical inflammatory distinguishing phenotypes (high-grade vs. low-grade inflammation) defining outcomes this condition. Summary Pericarditis involves intense activity, which causes elevation different markers, such as C-reactive protein, erythrocyte sedimentation rate, neutrophils platelets, amyloid A D-Dimer. Conversely, lymphocytes are often reduced, well hemoglobin during phase. Cardiac troponins T I elevated up to 30% cases. Biomarker for CRP-negative cases is needed. Other markers proposed diagnosis prognosis IRAP, anti-heart antibodies anti-intercalated disk antibodies, but we need further validate them.

Язык: Английский

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Thrombotic microenvironment responsive crosslinking cyclodextrin metal-organic framework nanocarriers for precise targeting and thrombolysis

Carbohydrate Polymers, Год журнала: 2024, Номер 334, С. 122058 - 122058

Опубликована: Март 15, 2024

Язык: Английский

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Novel Therapeutics and Upcoming Clinical Trials Targeting Inflammation in Cardiovascular Diseases

Arteriosclerosis Thrombosis and Vascular Biology, Год журнала: 2024, Номер 44(12), С. 2371 - 2395

Опубликована: Окт. 10, 2024

Cardiovascular disease (CVD) remains a major health burden despite significant therapeutic advances accomplished over the last decades. It is widely and increasingly recognized that systemic inflammation not only represents cardiovascular risk prognostic factor but also plays key pathogenic roles in CVD development progression. Despite compelling preclinical evidence suggesting large potential of anti-inflammatory pharmacological interventions across numerous CVDs, clinical translation incomplete, mainly due to (1) yet undefined molecular signaling; (2) challenges safety efficacy profile drugs; (3) difficulties identifying optimal patient candidates responders therapeutics, as well windows. Randomized controlled trials demonstrated safety/efficacy canakinumab colchicine secondary prevention, providing confirmation for involvement specific inflammatory pathway (NLRP3 [NACHT, LRR, PYD domain-containing protein 3] inflammasome/IL [interleukin]-1β) atherosclerotic CVD. Colchicine was recently approved by US Food Drug Administration this indication. Diverse drugs targeting distinct pathways are used management other CVDs including myocarditis pericarditis. Ongoing research efforts directed implementing strategies growing number through repurposing available novel compounds, which herein concisely discussed. This review summarizes main characteristics findings completed upcoming randomized directly discusses future perspectives exciting constantly expanding landscape cardioimmunology.

Язык: Английский

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Monocyte/macrophage-mediated venous thrombus resolution

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Июль 19, 2024

Venous thromboembolism (VTE) poses a notable risk of morbidity and mortality. The natural resolution the venous thrombus might be potential alternative treatment strategy for VTE. Monocytes/macrophages merge as pivotal cell types in gradual thrombus. In this review, vital role macrophages inducing inflammatory response, augmenting neovascularization, facilitating degradation fibrin collagen during was described. two phenotypes involved their dual functions were discussed. Macrophages expressing various factors, including cytokines receptors, adhesion molecules, chemokine vascular endothelial growth factor profibrinolytic- or antifibrinolytic-related enzymes, other elements, are explored to promote attenuate resolution. Furthermore, review provides comprehensive summary new promising therapeutic candidate drugs associated with monocytes/macrophages that have been demonstrated impair However, further clinical trials essential validate efficacy VTE therapy.

Язык: Английский

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Connecting the Dots: NLRP3 Inflammasome as a Key Mediator in the Intersection of Depression and Cardiovascular Disease – A Narrative Review

Heart and Mind, Год журнала: 2025, Номер unknown

Опубликована: Янв. 10, 2025

Abstract Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide and frequently coexist with depressive disorders. The consequence their concurrence is exacerbation both conditions. Numerous studies seek to understand pathophysiological connection between this mental disorder CVDs, theories such as autonomic dysfunction, endocrine dysregulation, platelet inflammation have been suggested. However, in review, we propose that these all related etiology can be explained by involvement nucleotide-binding oligomerization domain-, leucine-rich repeat-, pyrin domain-containing protein 3 (NLRP3) inflammasome-mediated inflammation. To elucidate, investigate inflammasome contribution central nervous system (CNS), vasculature, heart, system. We presented evidence neurotransmitter imbalances, hypothalamic pituitary adrenal axis microglial activation, inflammatory damage CNS. put forward research on NLRP3 activation showing vascular could alter brain blood barrier, endothelial lipid metabolism, hypertension, atherosclerosis, aneurisms, hypercoagulable states. Similarly, explore its development heart failure, cardiac remodeling, myocardial infarction, arrythmias, hyperactive tuning sympathetic response.

Язык: Английский

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Altered fibrin clot properties and elevated von Willebrand factor are associated with progression to permanent atrial fibrillation: A cohort study

European Journal of Clinical Investigation, Год журнала: 2025, Номер unknown

Опубликована: Янв. 20, 2025

Abstract Background The role of a prothrombotic state in atrial fibrillation (AF) progression to permanent arrythmia (PerAF) is unclear. Formation denser and poorly lysable fibrin clots has been observed AF patients also with sinus rhythm association higher stroke risk. We investigated whether altered clot properties other markers may contribute transition PerAF. Methods In the cohort study, 226 anticoagulated (median age 69 years, median CHA 2 DS ‐VASc 3) paroxysmal ( n = 83, 36.7%) or persistent 143, 63.3%) AF, we assessed at baseline plasma permeability (K s ), lysis time (CLT), proteins involved fibrinolysis von Willebrand factor (vWF) antigen. recorded PerAF during follow‐up 58 months. Results During follow‐up, was documented 62 (27.4%, 5.7%/year) subjects, who had prevalence heart failure, body mass index longer history arrhythmia. associated 25.7% CLT relation 21.3% plasminogen activator inhibitor type 1, 29% vWF compared remainder, no differences K , α2‐antiplasmin. By multivariable analysis, (per 10 min, odds ratio [OR] 2.734, 95% confidence interval [CI] 1.788–4.180, p < .001), 10%, OR 1.352, CI 1.145–1.596, .001) failure (OR 2.637, 1.008–6.900, .048) were Conclusion Suppressed susceptibility elevated could despite anticoagulation, which suggests links between blood coagulation progression.

Язык: Английский

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High levels of soluble neuropilin -1 in critically ill multiple trauma/surgical patients

Advances in Medical Sciences, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

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Cognitive Sequelae of COVID‐19: Mechanistic Insights and Therapeutic Approaches

CNS Neuroscience & Therapeutics, Год журнала: 2025, Номер 31(3)

Опубликована: Март 1, 2025

ABSTRACT Background The COVID‐19 pandemic has left an indelible mark on the world, with mounting evidence suggesting that it not only posed acute challenges to global healthcare systems but also unveiled a complex array of long‐term consequences, particularly cognitive impairment (CI). As persistence post‐COVID‐19 neurological syndrome could evolve into next public health crisis, is imperative gain better understanding intricate pathophysiology CI in patients and viable treatment strategies. Methods This comprehensive review explores management across phases COVID‐19, from infection Long‐COVID, by synthesizing findings clinical, preclinical, mechanistic studies identify key contributors CI, as well current therapeutic approaches. Results Key mechanisms contributing include persistent neuroinflammation, cerebrovascular complications, direct neuronal injury, activation kynurenine pathway, psychological distress. Both pharmacological interventions, such anti‐inflammatory therapies agents targeting neuroinflammatory pathways, non‐pharmacological strategies, including rehabilitation, show promise addressing these challenges. Although much derived preclinical animal studies, provide foundational insights potential Conclusion By knowledge, this highlights importance COVID‐19‐related offers actionable for mitigation recovery community continues grapple pandemic's impact.

Язык: Английский

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