NLRP3-Induced NETosis: A Potential Therapeutic Target for Ischemic Thrombotic Diseases?

Rahul Kumar; Gokul Patil; Sanjana Dayal

doi:10.3390/cells12232709

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NLRP3-Induced NETosis: A Potential Therapeutic Target for Ischemic Thrombotic Diseases?

Journal article

Open access

Peer reviewed

NLRP3-Induced NETosis: A Potential Therapeutic Target for Ischemic Thrombotic Diseases?

Rahul Kumar, Gokul Patil and Sanjana Dayal

Cells (Basel, Switzerland), Vol.12(23), 2709

01/01/2023

DOI: 10.3390/cells12232709

PMCID: PMC10706381

PMID: 38067137

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Abstract

Ischemic thrombotic disease, characterized by the formation of obstructive blood clots within arteries or veins, is a condition associated with life-threatening events, such as stroke, myocardial infarction, deep vein thrombosis, and pulmonary embolism. The conventional therapeutic strategy relies on treatments with anticoagulants that unfortunately pose an inherent risk of bleeding complications. These anticoagulants primarily target clotting factors, often overlooking upstream events, including the release of neutrophil extracellular traps (NETs). Neutrophils are integral components of the innate immune system, traditionally known for their role in combating pathogens through NET formation. Emerging evidence has now revealed that NETs contribute to a prothrombotic milieu by promoting platelet activation, increasing thrombin generation, and providing a scaffold for clot formation. Additionally, NET components enhance clot stability and resistance to fibrinolysis. Clinical and preclinical studies have underscored the mechanistic involvement of NETs in the pathogenesis of thrombotic complications, since the clots obtained from patients and experimental models consistently exhibit the presence of NETs. Given these insights, the inhibition of NETs or NET formation is emerging as a promising therapeutic approach for ischemic thrombotic diseases. Recent investigations also implicate a role for the nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome as a mediator of NETosis and thrombosis, suggesting that NLRP3 inhibition may also hold potential for mitigating thrombotic events. Therefore, future preclinical and clinical studies aimed at identifying and validating NLRP3 inhibition as a novel therapeutic intervention for thrombotic disorders are imperative.

Aging

Blood Coagulation

Diabetes

Disease

Immune System

Ischemia

Pathogenesis

Thrombosis

Age

Anticoagulants

Arteries

Blood platelets

Cerebral infarction

Clotting

Coronaviruses

Embolism

Fibrinolysis

Glycoproteins

Heart attacks

Hormone replacement therapy

Inflammasomes

Innate immunity

Leukocytes (neutrophilic)

Myocardial infarction

Neutrophils

Oligomerization

Plasma

Pyrin protein

Risk factors

Therapeutic targets

Thrombin

Details

Title: Subtitle: NLRP3-Induced NETosis: A Potential Therapeutic Target for Ischemic Thrombotic Diseases?
Creators: Rahul Kumar - University of Iowa
Gokul Patil
Sanjana Dayal - University of Iowa
Resource Type: Journal article
Publication Details: Cells (Basel, Switzerland), Vol.12(23), 2709
DOI: 10.3390/cells12232709
PMID: 38067137
PMCID: PMC10706381
NLM abbreviation: Cells
eISSN: 2073-4409
Publisher: MDPI AG
Grant note: name: National Institutes of Health, award: AI162778; name: Office of Research and Development and Department of Veterans Affairs, award: I01CX001932
Language: English
Date published: 01/01/2023
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
Record Identifier: 9984520458902771

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