Toll-like receptor expression and apoptosis morphological patterns in female rat hearts with takotsubo syndrome induced by isoprenaline

Kołodzińska, Agnieszka; Czarzasta, Katarzyna; Szczepankiewicz, Benedykt; Główczyńska, Renata; Fojt, Anna; Ilczuk, Tomasz; Budnik, Monika; Krasuski, Krzysztof; Folta, Miłosz; Cudnoch-Jędrzejewska, Agnieszka; Górnicka, Barbara; Opolski, Grzegorz

doi:10.1016/j.lfs.2018.02.042

Cited by 21 publications

(26 citation statements)

References 40 publications

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“…Sachdeva et al [12] calcineurin signaling activation that leads to hypertrophy [22]. TLR4 expression in cardiomyocytes was previously documented [21]. Timmers et al [23] observed that TLR4…”

Section: Discussionmentioning

confidence: 97%

“…Foci were the most numerous in central and endocardial heart muscle layers, rarely appearing in epicardial zone. In the foci TLR2, TLR4, TLR6 positive mononuclear cells and TLR4CD68 as well as TLR6CD68 positive cells were distinguishable [ 21 ]. Apoptosis concerned singles cardiomyocytes 24 h post-ISO, inflammatory cells in the whole course of TTS, and endothelial cells of the vessels 7 days post-ISO [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

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Isoprenaline induced Takotsubo syndrome: Histopathological analyses of female rat hearts

et al. 2022

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Background: Takotsubo syndrome (TTS) is a stress-induced disorder affecting mostly postmenopausal women. The aim of the study was to evaluate isoprenaline (ISO) dependent female rat model and histopathological characteristics in TTS. Methods: Forty-nine Sprague Dawley female rats, 12 weeks old, were injected intraperitoneally with a single dose of ISO at doses 50 (n = 8), 75 (n = 6), 100 (n = 3), 150 (n = 27) and 200 (n = 5) mg/kg body weight (bw). The control group (n = 6) was injected with physiological saline. The echocardiographic examination to assess wall motion abnormalities took place 24, 48, 72 h, and 7 days post-ISO. Histopathological analysis was performed on the basis of hematoxylin-eosin staining. Results: The total mortality rate was 3/49 (6.12%). The optimum dose of ISO to induce TTS was 150 mg/kg bw and 21/27 (77.77%) rats showed apical ballooning. Histopathological analysis revealed focal necrosis/apoptosis of cardiomyocytes with inflammatory and fibroblast-like cell infiltration. Foci were the most numerous in the central muscle layer with apical-basal gradient 24,48,72 h post-ISO (p < 0.05). Significant differences were noted 48 h post-ISO in the central layer in apical vs basal segments (p = 0.0032), in the endocardial layer in apical vs basal segments (0.00024) and in mid-cavital vs. basal segments (p = 0.0483). The number of foci in endocardium of apical region differ 48 h post-ISO in rats with a dose of 150 vs. 200 mg/kg bw (p = 0.0084). Conclusions: The ISO female rat model of TTS is associated with higher optimum dose and lower mortality in comparison with the male TTS model. TTS presents as a singles cardiomyocyte disorder, foci concerned mainly central muscle layer with apical-basal gradient.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Isoprenaline induced Takotsubo syndrome: Histopathological analyses of female rat hearts

et al. 2022

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“…TLR4 initiates the expression of a number of pro-inflammatory genes, cell surface molecules, and chemokines, exacerbating myocardium damage [1]. In a rat model of post-infarct heart failure (HF), TLR4 mRNA expression and protein levels were increased in the infarcted and remote myocardium [14]. Additionally, TLR2 was also identified as a death receptor, promoting apoptosis, mediated heart motion abnormalities, inflammation, and fibrosis in MI and HF [14].…”

Section: Introductionmentioning

confidence: 99%

β-Caryophyllene as a Potential Protective Agent Against Myocardial Injury: The Role of Toll-Like Receptors

Younis

Mohamed

2019

Molecules

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Myocardial infarction (MI) remains one of the major causes of mortality around the world. A possible mechanism involved in myocardial infarction is the engagement of Toll-like receptors (TLRs). This study was intended to discover the prospective cardioprotective actions of β-caryophyllene, a natural sesquiterpene, to ameliorate isoproterenol (ISO)-induced myocardial infarction through HSP-60/TLR/MyD88/NFκB pathway. β-Caryophyllene (100 or 200 mg/kg/day orally) was administered for 21 days then MI was induced via ISO (85 mg/kg, subcutaneous) on 20th and 21st days. The results indicated that ISO induced a significant infarcted area associated with several alterations in the electrocardiogram (ECG) and blood pressure (BP) indices and caused an increase in numerous cardiac indicators such as creatine phosphokinase (CPK), creatine kinase-myocardial bound (CK-MB), lactate dehydrogenase (LDH), and cardiac tropinine T (cTnT). In addition, ISO significantly amplified heat shock protein 60 (HSP-60) and other inflammatory markers, such as TNF-α, IL-Iβ, and NFκB, and affected TLR2 and TLR4 expression and their adaptor proteins; Myeloid differentiation primary response 88 (MYD88), and TIR-domain-containing adapter-inducing interferon-β (TRIF). On the other hand, consumption of β-caryophyllene significantly reversed the infarcted size, ECG and BP alterations, ameliorated the ISO elevation in cardiac indicators; it also notably diminished HSP-60, and subsequently TLR2, TLR4, MYD88, and TRIF expression, with a substantial reduction in inflammatory mediator levels. This study revealed the cardioprotective effect of β-caryophyllene against MI through inhibiting HSP-60/TLR/MyD88/NFκB signaling pathways.

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“…Recent evidence indicated that TTS patients suffered from acute endogenous catecholamine release, which may trigger oxidative stress and inflammation. The apoptosis of inflammatory cells was visible in the whole course of TTS, while the apoptosis of endothelial cells appeared only in the recovery phase [196]. ISO significantly increased the levels of reactive oxygen species (ROS) in the setting of TTS, leading to the injury of myocardial cells, mitochondrial dysfunction, acute Ca 2+ overload, TLR4/NF-κB signaling alterations, dysregulation of the glucose and lipid metabolic pathways represented by decreases in the final glycolytic and β-oxidation metabolites and reduced availability of Krebs cycle intermediates.…”

Section: Animal Models and Mechanistic Studiesmentioning

confidence: 94%

Takotsubo Syndrome: Translational Implications and Pathomechanisms

Fan

Yang

Kowitz

et al. 2022

IJMS

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Takotsubo syndrome (TTS) is identified as an acute severe ventricular systolic dysfunction, which is usually characterized by reversible and transient akinesia of walls of the ventricle in the absence of a significant obstructive coronary artery disease (CAD). Patients present with chest pain, ST-segment elevation or ischemia signs on ECG and increased troponin, similar to myocardial infarction. Currently, the known mechanisms associated with the development of TTS include elevated levels of circulating plasma catecholamines and their metabolites, coronary microvascular dysfunction, sympathetic hyperexcitability, inflammation, estrogen deficiency, spasm of the epicardial coronary vessels, genetic predisposition and thyroidal dysfunction. However, the real etiologic link remains unclear and seems to be multifactorial. Currently, the elusive pathogenesis of TTS and the lack of optimal treatment leads to the necessity of the application of experimental models or platforms for studying TTS. Excessive catecholamines can cause weakened ventricular wall motion at the apex and increased basal motion due to the apicobasal adrenoceptor gradient. The use of beta-blockers does not seem to impact the outcome of TTS patients, suggesting that signaling other than the beta-adrenoceptor-associated pathway is also involved and that the pathogenesis may be more complex than it was expected. Herein, we review the pathophysiological mechanisms related to TTS; preclinical TTS models and platforms such as animal models, human-induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) models and their usefulness for TTS studies, including exploring and improving the understanding of the pathomechanism of the disease. This might be helpful to provide novel insights on the exact pathophysiological mechanisms and may offer more information for experimental and clinical research on TTS.

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Toll-like receptor expression and apoptosis morphological patterns in female rat hearts with takotsubo syndrome induced by isoprenaline

Cited by 21 publications

References 40 publications

Isoprenaline induced Takotsubo syndrome: Histopathological analyses of female rat hearts

Isoprenaline induced Takotsubo syndrome: Histopathological analyses of female rat hearts

β-Caryophyllene as a Potential Protective Agent Against Myocardial Injury: The Role of Toll-Like Receptors

Takotsubo Syndrome: Translational Implications and Pathomechanisms

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