Etosis, rather than apoptosis or cell proliferation, typifies thrombus progression – An immunohistochemical study of coronary aspirates

Background: Coronary thrombosis is a process with unpredictable clinical outcome. Changes of thrombus composition overtime influence tissue repair and stabilization. We investigated rates of cell deaths and cell proliferation at different time points after initiation of thrombosis. Methods: Thrombec...

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Main Authors: Kartika R. Pertiwi, Onno J. de Boer, Pauline A.M. Gabriels, Allard C. van der Wal
Format: Article
Language:English
Published: Elsevier 2020-02-01
Series:International Journal of Cardiology: Heart & Vasculature
Online Access:http://www.sciencedirect.com/science/article/pii/S2352906719301976
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spelling doaj-b2fa816e92ba4778b421c4fd2aae0a342020-11-25T03:09:21ZengElsevierInternational Journal of Cardiology: Heart & Vasculature2352-90672020-02-0126Etosis, rather than apoptosis or cell proliferation, typifies thrombus progression – An immunohistochemical study of coronary aspiratesKartika R. Pertiwi0Onno J. de Boer1Pauline A.M. Gabriels2Allard C. van der Wal3Department of Pathology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, Netherlands; Department of Biology Education, Faculty of Mathematics and Natural Science, Yogyakarta State University, Jl. Colombo No. 1, Karang Malang, Caturtunggal, Kec. Depok, Kabupaten Sleman, Daerah Istimewa Yogyakarta 55281, IndonesiaDepartment of Pathology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, NetherlandsDepartment of Pathology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, NetherlandsDepartment of Pathology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, Netherlands; Corresponding author.Background: Coronary thrombosis is a process with unpredictable clinical outcome. Changes of thrombus composition overtime influence tissue repair and stabilization. We investigated rates of cell deaths and cell proliferation at different time points after initiation of thrombosis. Methods: Thrombectomy aspirates of 55 myocardial infarction patients were selected and histomorphologically classified as fresh (25), lytic (25), partially fibrocellular (10), completely fibrocellular (10). Paraffin sections were immunostained with anti-(cleaved) caspase-3/Casp3 (apoptosis), Citrullinated histone/CitH 3 (etosis), C-reactive protein/CRP and Ki67 (proliferation) in combination with either Feulgen counterstaining (DNA) or cell markers for granulocytes, macrophages, SMCs, platelets and endothelium. Rates of apoptosis, etosis and proliferation were measured as a percentage of total number of immunopositive pixels versus total number of DNA positive pixels, while co-localization with cell markers was assessed by digital image analysis. Results: Positive staining of CitH3 was observed more frequently (93%) than Casp3 (70%), Ki67 (79%) or CRP (59%) (p < 0.05). Moreover, rate of etosis, found in granulocytes and macrophages, differed significantly among thrombi of different age, being higher in lytic (12.82) than in fresh (8.52) and late-organized (2.75) (p < 0.05). Such differences were not observed for the rates of apoptosis or cell proliferation related to thrombus age. CRP staining was present in fresh, lytic and organized thrombi, but did not reliably identify necrotic areas. Conclusions: Different patterns of cell death and cell proliferation are noticed during progression of coronary thrombus overtime, but with significant differences for only etosis. Etosis could potentially serve as a biomarker for thrombus instability with clinical significance. Keywords: Acute myocardial infarction, Coronary thrombosis, Cell death, Apoptosis, Etosis, Cell proliferationhttp://www.sciencedirect.com/science/article/pii/S2352906719301976
collection DOAJ
language English
format Article
sources DOAJ
author Kartika R. Pertiwi
Onno J. de Boer
Pauline A.M. Gabriels
Allard C. van der Wal
spellingShingle Kartika R. Pertiwi
Onno J. de Boer
Pauline A.M. Gabriels
Allard C. van der Wal
Etosis, rather than apoptosis or cell proliferation, typifies thrombus progression – An immunohistochemical study of coronary aspirates
International Journal of Cardiology: Heart & Vasculature
author_facet Kartika R. Pertiwi
Onno J. de Boer
Pauline A.M. Gabriels
Allard C. van der Wal
author_sort Kartika R. Pertiwi
title Etosis, rather than apoptosis or cell proliferation, typifies thrombus progression – An immunohistochemical study of coronary aspirates
title_short Etosis, rather than apoptosis or cell proliferation, typifies thrombus progression – An immunohistochemical study of coronary aspirates
title_full Etosis, rather than apoptosis or cell proliferation, typifies thrombus progression – An immunohistochemical study of coronary aspirates
title_fullStr Etosis, rather than apoptosis or cell proliferation, typifies thrombus progression – An immunohistochemical study of coronary aspirates
title_full_unstemmed Etosis, rather than apoptosis or cell proliferation, typifies thrombus progression – An immunohistochemical study of coronary aspirates
title_sort etosis, rather than apoptosis or cell proliferation, typifies thrombus progression – an immunohistochemical study of coronary aspirates
publisher Elsevier
series International Journal of Cardiology: Heart & Vasculature
issn 2352-9067
publishDate 2020-02-01
description Background: Coronary thrombosis is a process with unpredictable clinical outcome. Changes of thrombus composition overtime influence tissue repair and stabilization. We investigated rates of cell deaths and cell proliferation at different time points after initiation of thrombosis. Methods: Thrombectomy aspirates of 55 myocardial infarction patients were selected and histomorphologically classified as fresh (25), lytic (25), partially fibrocellular (10), completely fibrocellular (10). Paraffin sections were immunostained with anti-(cleaved) caspase-3/Casp3 (apoptosis), Citrullinated histone/CitH 3 (etosis), C-reactive protein/CRP and Ki67 (proliferation) in combination with either Feulgen counterstaining (DNA) or cell markers for granulocytes, macrophages, SMCs, platelets and endothelium. Rates of apoptosis, etosis and proliferation were measured as a percentage of total number of immunopositive pixels versus total number of DNA positive pixels, while co-localization with cell markers was assessed by digital image analysis. Results: Positive staining of CitH3 was observed more frequently (93%) than Casp3 (70%), Ki67 (79%) or CRP (59%) (p < 0.05). Moreover, rate of etosis, found in granulocytes and macrophages, differed significantly among thrombi of different age, being higher in lytic (12.82) than in fresh (8.52) and late-organized (2.75) (p < 0.05). Such differences were not observed for the rates of apoptosis or cell proliferation related to thrombus age. CRP staining was present in fresh, lytic and organized thrombi, but did not reliably identify necrotic areas. Conclusions: Different patterns of cell death and cell proliferation are noticed during progression of coronary thrombus overtime, but with significant differences for only etosis. Etosis could potentially serve as a biomarker for thrombus instability with clinical significance. Keywords: Acute myocardial infarction, Coronary thrombosis, Cell death, Apoptosis, Etosis, Cell proliferation
url http://www.sciencedirect.com/science/article/pii/S2352906719301976
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