Neutrophilic leukocytes and neutrophil extracellular traps in native aortic valve endocarditis
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Date
2023
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Rīgas Stradiņa universitāte
Rīga Stradiņš University
Rīga Stradiņš University
Abstract
Infekciozais endokardīts ir slimība, kas skar endokardu, tai skaitā arī sirds vārstuļus. Aortas vārstulis ir viens no visbiežāk skartajiem vārstuļiem. Infekciozā endokardīta patoģenēzē būtiska loma ir bakterēmijai un vārstuļu endotēlija bojājumam, taču pētījumi liecina, ka būtiska nozīme var būt arī vārstuļu lapiņas neitrofilo leikocītu infiltrācijai un to ārpusšūnu lamatām (angl. neutrophil extracellular traps). Šī pētījuma mērķis bija analizēt neitrofilo leikocītu un neitrofilo leikocītu ārpusšūnu lamatu izplatību gaismas mikroskopijā ar rutīnas krāsošanas un imūnhistoķīmijas metodēm aortas vārstuļa audos un veģetācijās pacientiem ar aortas vārstuļa infekciozo endokardītu. Statistiski nozīmīgas atšķirības novērotas, salīdzinot vārstuļa daļas, respektīvi, lielākā neitrofilo leikocītu infiltrācija tika novērota lapiņas brīvajā malā (vidējais 5.89 ± 3.00, p<0.001) un vidusdaļā (vidējais 4.58 ± 3.64, p=0.032), salīdzinot ar bazālo jeb aortas sienai tuvāko daļu (2.05 ± 1.90). Netika novērtas statistiski nozīmīgas atšķirības neitrofilo leikocītu infiltrācijā, sadalot vārstuli pa morfoloģiskajiem slāņiem – fibrosa, spongiosa, ventricularis. Izmantojot imūnhistoķīmijas metodes, tika vizualizēti neitrofilo leikocītu ārpusšūnu lamatu struktūrelementi – mieloperoksidāze un citrulinēti histoni H3. Tika novērota abu antivielu pozitīva ekspresija infekciozā endokardīta skartās aortālās vārstules lapiņā un lielākoties veģetāciju struktūrā.
Šis pētījums apstiprina ideju, ka vārstuļa lapiņas brīvā mala un vidējā daļa ir pakļauta pastiprinātai asins plūsmai; endotēlija bojājums un veģetāciju veidošānās visticamāk notiek kopā ar infekciozu endokardītu saistītu bakterēmiju.
Infective endocarditis is a disease that affects the endocardium and often alters the heart valves, notably aortic valve. Bacteremia and valvular endothelial damage play an essential role in the pathogenesis of infective endocarditis. Pertinent literature suggests that neutrophil extracellular traps are important contributors to the development of the disease. However, largely peculiarities of the valvular damage and contribution of neutrophils to the alteration of cardiac tissue are not explored sufficiently. The purpose of this study was to investigate the occurrence and distribution of neutrophilic leukocytes and neutrophil extracellular traps in the native aortic valves affected by infective endocarditis using histopathology and immunohistochemistry assays. In addition, the presence of vegetations on the heart valve were analysed. Infiltration of neutrophils into the valvular leaflet was significantly more severe at the free margin (mean 5.89 ± 3.00, p<0.001) and the middle portion (mean 4.58 ± 3.64, p=0.032) when compared to the base portion (2.05 ± 1.90). No significant differences in neutrophilic leukocyte infiltrating inflammatory lesions were found when the cusp layers were compared. The presence of myeloperoxidase and citrullinated histones’ expression characteristic of neutrophil extracellular traps was demonstrated in IE-affected valvular leaflets and vegetations by the use of immunohistochemistry. Collectively, the study results suggest that the free cusp margin and its middle portion of the aortic valve are exposed to enforced blood flow; endothelial damage and vegetation formation are likely to occurr along with the presence of infective endocarditis-related bacteraemia.
Infective endocarditis is a disease that affects the endocardium and often alters the heart valves, notably aortic valve. Bacteremia and valvular endothelial damage play an essential role in the pathogenesis of infective endocarditis. Pertinent literature suggests that neutrophil extracellular traps are important contributors to the development of the disease. However, largely peculiarities of the valvular damage and contribution of neutrophils to the alteration of cardiac tissue are not explored sufficiently. The purpose of this study was to investigate the occurrence and distribution of neutrophilic leukocytes and neutrophil extracellular traps in the native aortic valves affected by infective endocarditis using histopathology and immunohistochemistry assays. In addition, the presence of vegetations on the heart valve were analysed. Infiltration of neutrophils into the valvular leaflet was significantly more severe at the free margin (mean 5.89 ± 3.00, p<0.001) and the middle portion (mean 4.58 ± 3.64, p=0.032) when compared to the base portion (2.05 ± 1.90). No significant differences in neutrophilic leukocyte infiltrating inflammatory lesions were found when the cusp layers were compared. The presence of myeloperoxidase and citrullinated histones’ expression characteristic of neutrophil extracellular traps was demonstrated in IE-affected valvular leaflets and vegetations by the use of immunohistochemistry. Collectively, the study results suggest that the free cusp margin and its middle portion of the aortic valve are exposed to enforced blood flow; endothelial damage and vegetation formation are likely to occurr along with the presence of infective endocarditis-related bacteraemia.
Description
Medicīna
Medicine
Veselības aprūpe
Health Care
Medicine
Veselības aprūpe
Health Care
Keywords
Infekciozais endokardīts, neitrofilu ekstracelulārie tīkli, imūnhistoķīmija, Infective endocarditis, neutrophil extracellular traps, immunohistochemistry