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在低温死亡的人心肌组织中过度表达;心脏死亡中与转录物和应激激素水平的关联。

is overexpressed in human cardiac tissue in hypothermia deaths; associations between the transcript and stress hormone levels in cardiac deaths.

机构信息

Research Unit of Biomedicine and Internal Medicine, Department of Forensic Medicine, Medical Research Center Oulu, University of Oulu, Oulu, Finland.

Forensic Medicine Unit, Finnish Institute for Health and Welfare, Oulu, Finland.

出版信息

Ann Med. 2024 Dec;56(1):2420862. doi: 10.1080/07853890.2024.2420862. Epub 2024 Nov 7.

Abstract

BACKGROUND

Amphiregulin (AREG) is a growth factor linked to cardioprotection and heart pathology during myocardial stress. Our aim was to investigate cardiac expression, its potential as a postmortem hypothermia marker and its possible stress hormone dependency in different types of deaths.

MATERIALS AND METHODS

Heart RNA was isolated from hypothermic, cardiac and non-cardiac deaths. Relative mRNA levels and urine stress hormone concentrations were measured by qPCR and enzyme-linked immunosorbent assays from eight different death cause groups. Receiver operating characteristic curve was used to evaluate a cut-off point for expression as a hypothermia marker. Regulatory elements were predicted by PROMO.

RESULTS

The mRNA levels were significantly higher in hypothermic deaths than in most cardiac and non-cardiac deaths. expression indicated hypothermic deaths with nearly 70% sensitivity and specificity. However, high expression levels were also detected in non-ischaemic deaths. The highest concentrations of adrenaline and cortisol were detected in hypothermic deaths, while the highest noradrenaline concentrations associated with atherosclerotic heart disease (AHD) deaths with acute myocardial infarction and trauma deaths. There were no significant correlations between stress hormones and mRNA in hypothermic and non-cardiac deaths, whereas moderate-to-high associations were detected in cardiac deaths. Putative response elements for cortisol and catecholamines were found in .

CONCLUSIONS

Severe hypothermia activates cardiac expression practicable as a postmortem hypothermia marker. Cortisol and catecholamines may act as transcriptional modifiers of this gene, especially in long-term ischaemic heart disease. However, the exact role of these hormones in upregulation of during hypothermia remains unclear.

摘要

背景

Amphiregulin(AREG)是一种与心肌应激时的心脏保护和心脏病理学相关的生长因子。我们的目的是研究心脏表达,其作为死后低温标志物的潜力及其在不同类型死亡中的潜在应激激素依赖性。

材料和方法

从低温、心脏和非心脏死亡中分离心脏 RNA。通过 qPCR 和酶联免疫吸附试验从八个不同死因组测量相对 mRNA 水平和尿液应激激素浓度。使用接收者操作特征曲线评估作为低温标志物的表达的截止点。通过 PROMO 预测调节元件。

结果

在低温死亡中,mRNA 水平明显高于大多数心脏和非心脏死亡。表达表明低温死亡的敏感性和特异性接近 70%。然而,在非缺血性死亡中也检测到高表达水平。在低温死亡中检测到肾上腺素和皮质醇的浓度最高,而在伴有急性心肌梗死和创伤死亡的动脉粥样硬化性心脏病(AHD)死亡中检测到最高的去甲肾上腺素浓度。在低温和非心脏死亡中,应激激素与 mRNA 之间没有显著相关性,而在心脏死亡中检测到中度至高度相关性。在 中发现了皮质醇和儿茶酚胺的推定反应元件。

结论

严重低温激活心脏表达,可作为死后低温标志物。皮质醇和儿茶酚胺可能作为该基因的转录修饰物起作用,特别是在长期缺血性心脏病中。然而,这些激素在低温期间上调的的确切作用仍不清楚。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3680/11544741/1026f790c556/IANN_A_2420862_F0001_B.jpg

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