First Department of Cardiology, Medical University of Warsaw, 1a Banacha St, 02-097 Warsaw, Poland.
Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, 1b Banacha St, 02-097 Warsaw, Poland.
Life Sci. 2018 Apr 15;199:112-121. doi: 10.1016/j.lfs.2018.02.042. Epub 2018 Mar 1.
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).
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.
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 (TLR2) was observed: 24, 48, 72 h post-ISO; TLR4 - 48 and 72 h post-ISO; TLR6 - 48 h post-ISO. Whereas in cardiomyocytes of remote myocardium: TLR2 - 72 h post-ISO; TLR4 - 24 and 72 h post-ISO; TLR6 - 24 h post-ISO. TLR2 mRNA was down-regulated 48 and 72 h post-ISO whereas TLR4 up-regulated 7 days post-ISO.
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.
Toll 样受体（TLR）和细胞凋亡被认为是心力衰竭的重要因素。我们的目的是描述 Takotsubo 综合征（TTS）模型中雌性大鼠心脏细胞凋亡、TLR2、TLR4 和 TLR6 表达的形态模式。
60 只 Sprague-Dawley 雌性大鼠单次腹腔注射 150mg/kg 体重的异丙肾上腺素（ISO）或 0.9%NaCl（对照）。在 ISO 注射后 24、48、72 小时和 7 天收集心脏。32/60 只心脏用于免疫组织病理学研究，28/60 只心脏用于实时研究。
ISO 后 24 小时在心肌细胞中观察到凋亡，24、48、72 小时和 7 天在浸润性炎症细胞中观察到凋亡，7 天在血管内皮细胞中观察到凋亡。在 TTS 的急性和恢复期均观察到弥漫性 TLR4CD68（CD68，一种巨噬细胞标志物）和 TLR6CD68 阳性细胞以及 TLR2、TLR4、TL6 单核细胞。在 TTS 中位于损伤（坏死/凋亡）心肌细胞附近的病灶中，观察到 TLR2（TLR2）蛋白高（强）表达：ISO 后 24、48、72 小时；TLR4-48 和 72 小时后 ISO；TLR6-48 小时后 ISO。而在远程心肌细胞中的 TLR2-ISO 后 72 小时；TLR4-ISO 后 24 和 72 小时；TLR6-ISO 后 24 小时。TLR2mRNA 在 ISO 后 48 和 72 小时下调，而 TLR4 在 ISO 后 7 天上调。
与对照大鼠相比，TTS 过程中细胞凋亡和 TLR 的表达模式不同。我们假设先天免疫和细胞凋亡可能在 TTS 病理生理学中发挥关键作用。
