Diagnostic and Prognostic Value of Neutrophil Extracellular Trap Levels in Patients With Acute Aortic Dissection

Abstract

BackgroundAcute aortic dissection (AAD) is a fatal disease demanding prompt diagnosis and proper treatment. There is a lack of serum markers that can effectively assist diagnosis and predict prognosis of AAD patients.MethodsNinety-six AAD patients were enrolled in this study, and 249 patients with chest pain due to acute myocardial infarction, pulmonary embolism, intramural hematoma, angina or other causes and 80 healthy controls were included as control group and healthy control group. Demographics, biochemical and hematological data and risk factors were recorded as baseline characteristics. The 1-year follow-up data were collected and analyzed. The diagnostic performance and ability to predict disease severity and prognosis of NET components in serum and aortic tissue were evaluated.ResultsCirculating NET markers, citH3 (citrullination of histone 3), cell-free DNA (cfDNA) and nucleosomes, had good diagnostic value for AAD, with superior diagnostic performance to D-dimer in discriminating patients with chest pain due to other reasons in the emergency department. Circulating NET marker levels (i.e., citH3, cfDNA and nucleosomes) of AAD patients were significantly higher than that of control group and healthy control group. In addition, circulating NET markers levels were closely associated with the disease severity, in-hospital death and 1-year survival of AAD patients. Systolic blood pressure < 90 mmHg and serum citH3 levels were identified as independent risk factors for 1-year survival of AAD patients. Excessive NET components (i.e., neutrophil elastase and citH3) in the aortic tissue of AAD patient were significantly higher than that of healthy donor aortic tissue. The expression levels of granules and nuclear NET components were significantly higher in aortic tissue from AAD patients than controls.ConclusionsCirculating NET markers, citH3, cfDNA and nucleosomes, have significant diagnostic value and predictive value of disease severity and prognosis of AAD patients. The NETs components may constitute a useful diagnostic and prognostic marker in AAD patients.

The link between neutrophils, NETs, and NLRP3 inflammasomes: The dual effect of CD177 and its therapeutic potential in acute respiratory distress syndrome/acute lung injury

“…Their production is dependent on the activation of NADPH oxidase, alongside the release of elastase and MPO from neutrophil granules. NETs primarily comprise a network structure containing DNA, histones, granular proteins, and enzymes, such as CitH3, MPO, and MMP-9 [ 31 , 32 ]. Our findings suggest that in the ALI model, the CD177 antibody can reduce the levels of inflammatory factors, MPO, and ROS in mouse peripheral blood and BALF, thereby alleviating the inflammatory damage associated with ALI.…”

CD177 Inhibits Neutrophil Extracellular Trap Formation and Protects against Acute Pancreatitis in Mice

“…Moreover, neutrophils are principal phagocytes in the innate defense system, which ensnare and kill pathogens by releasing NETs. NETs are structures comprising chromatin and more than 20 kinds of primary and secondary granule proteins and enzymes, such as CitH3, MPO, and MMP-9 [ 27 , 28 ]. These granule proteins and enzymes are released into the extracellular space to kill pathogenic bacteria.…”

Role of Peptidylarginine Deiminase and Neutrophil Extracellular Traps in Injuries: Future Novel Diagnostics and Therapeutic Targets

“…CitH3 has potential as both a biomarker and a therapeutic target given its strong correlation with NETosis and injury (47,86). CitH3 has been studied in a variety of pathologies including pancreatitis (90), aortic dissection (91), and COVID-19 (92) as a marker with possible prognostic value. CitH3 has previously been studied as either an independent or confirmatory test for NETosis reflecting inflammation in most studies including for SCI (93) and burn (73,94).…”