Agnieszka Kołodzińska1, Katarzyna Czarzasta2, Benedykt Szczepankiewicz3, Renata Główczyńska4, Anna Fojt5, Tomasz Ilczuk6, Monika Budnik7, Krzysztof Krasuski8, Miłosz Folta9, Agnieszka Cudnoch-Jędrzejewska10, Barbara Górnicka11, Grzegorz Opolski12. 1. First Department of Cardiology, Medical University of Warsaw, 1a Banacha St, 02-097 Warsaw, Poland. Electronic address: aa.kolodzinska@wp.pl. 2. Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, 1b Banacha St, 02-097 Warsaw, Poland. Electronic address: kczarzasta@wum.edu.pl. 3. Department of Pathology, Medical University of Warsaw, 7 Pawińskiego St, 02-106 Warsaw, Poland. Electronic address: bszczepankiewicz@wum.edu.pl. 4. First Department of Cardiology, Medical University of Warsaw, 1a Banacha St, 02-097 Warsaw, Poland. Electronic address: renata.glowczynska@wum.edu.pl. 5. First Department of Cardiology, Medical University of Warsaw, 1a Banacha St, 02-097 Warsaw, Poland. Electronic address: anna.fojt@o2.pl. 6. Department of Pathology, Medical University of Warsaw, 7 Pawińskiego St, 02-106 Warsaw, Poland. Electronic address: tomasz.ilczuk@wum.edu.pl. 7. First Department of Cardiology, Medical University of Warsaw, 1a Banacha St, 02-097 Warsaw, Poland. Electronic address: moni.budnik@gmail.com. 8. Department of Medical Informatics and Telemedicine, Medical University of Warsaw, 1a Banacha St, 02-097 Warsaw, Poland; Faculty of Mathematics and Information Science, Warsaw University of Technology, 75 Koszykowa St, 00-662 Warsaw, Poland. Electronic address: kfk@go2.pl. 9. First Department of Cardiology, Medical University of Warsaw, 1a Banacha St, 02-097 Warsaw, Poland; Department of Pathology, Medical University of Warsaw, 7 Pawińskiego St, 02-106 Warsaw, Poland. Electronic address: miloszf21@gmail.com. 10. Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, 1b Banacha St, 02-097 Warsaw, Poland. Electronic address: agnieszka.cudnoch@wum.edu.pl. 11. Department of Pathology, Medical University of Warsaw, 7 Pawińskiego St, 02-106 Warsaw, Poland. Electronic address: barbara.gornicka@wum.edu.pl. 12. First Department of Cardiology, Medical University of Warsaw, 1a Banacha St, 02-097 Warsaw, Poland. Electronic address: Grzegorz.Opolski@wum.edu.pl.
Abstract
AIMS: Toll-like receptors (TLR) and apoptosis were indicated as important factors in heart failure. Our aim was to characterize the morphological pattern of apoptosis, TLR2, TLR4, and TLR6 expression in female rat hearts in the model of takotsubo syndrome (TTS). MAIN METHODS: 60 Sprague-Dawley female rats were treated with a single dose of 150 mg/kg b.wt. of isoprenaline (ISO) or 0.9% NaCl (controls). Hearts were collected 24, 48, 72 h and 7 days post-ISO injection. 32/60 hearts were used in immunohistopathological studies and 28/60 in real time. KEY FINDINGS: Apoptosis was observed 24 h post-ISO in cardiomyocytes, 24, 48, 72 h and 7 days post-ISO in infiltrating inflammatory cells, 7 days post-ISO in endothelial cells of vessels. Diffuse TLR4CD68 (CD68, a macrophage marker) and TLR6CD68 positive cells and TLR2, TLR4, TLR6 mononuclear cells were observed in both acute and recovery phase of TTS. In the foci located in the neighborhood of damaged (necrotic/apoptotic) cardiomyocytes in TTS, high (strong) protein expression of TLR2 (TLR2high) was observed: 24, 48, 72 h post-ISO; TLR4high - 48 and 72 h post-ISO; TLR6high - 48 h post-ISO. Whereas in cardiomyocytes of remote myocardium: TLR2high - 72 h post-ISO; TLR4high - 24 and 72 h post-ISO; TLR6high - 24 h post-ISO. TLR2 mRNA was down-regulated 48 and 72 h post-ISO whereas TLR4 up-regulated 7 days post-ISO. SIGNIFICANCE: The expression pattern of apoptosis and TLR differs in the course of TTS in comparison with the control rats. We hypothesize that innate immunity and apoptosis may play a crucial role in TTS pathophysiology.
AIMS: Toll-like receptors (TLR) and apoptosis were indicated as important factors in heart failure. Our aim was to characterize the morphological pattern of apoptosis, TLR2, TLR4, and TLR6 expression in female rat hearts in the model of takotsubo syndrome (TTS). MAIN METHODS: 60 Sprague-Dawley female rats were treated with a single dose of 150 mg/kg b.wt. of isoprenaline (ISO) or 0.9% NaCl (controls). Hearts were collected 24, 48, 72 h and 7 days post-ISO injection. 32/60 hearts were used in immunohistopathological studies and 28/60 in real time. KEY FINDINGS: Apoptosis was observed 24 h post-ISO in cardiomyocytes, 24, 48, 72 h and 7 days post-ISO in infiltrating inflammatory cells, 7 days post-ISO in endothelial cells of vessels. Diffuse TLR4CD68 (CD68, a macrophage marker) and TLR6CD68 positive cells and TLR2, TLR4, TLR6 mononuclear cells were observed in both acute and recovery phase of TTS. In the foci located in the neighborhood of damaged (necrotic/apoptotic) cardiomyocytes in TTS, high (strong) protein expression of TLR2 (TLR2high) was observed: 24, 48, 72 h post-ISO; TLR4high - 48 and 72 h post-ISO; TLR6high - 48 h post-ISO. Whereas in cardiomyocytes of remote myocardium: TLR2high - 72 h post-ISO; TLR4high - 24 and 72 h post-ISO; TLR6high - 24 h post-ISO. TLR2 mRNA was down-regulated 48 and 72 h post-ISO whereas TLR4 up-regulated 7 days post-ISO. SIGNIFICANCE: The expression pattern of apoptosis and TLR differs in the course of TTS in comparison with the control rats. We hypothesize that innate immunity and apoptosis may play a crucial role in TTS pathophysiology.
Authors: Ivana Fiserova; Minh Duc Trinh; Moustafa Elkalaf; Lukas Vacek; Marek Heide; Stanislava Martinkova; Kamila Bechynska; Vit Kosek; Jana Hajslova; Ondrej Fiser; Petr Tousek; Jan Polak Journal: Front Cardiovasc Med Date: 2022-08-22