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外泌体在脓毒症性心肌病中的双重作用

Dual Behavior of Exosomes in Septic Cardiomyopathy.

作者信息

Monteiro Valter Vinícius Silva, Reis Jordano Ferreira, de Souza Gomes Rafaelli, Navegantes Kely Campos, Monteiro Marta Chagas

机构信息

School of Pharmacy, Health Science Institute, Federal University of Pará/UFPA, Belém, PA, 66075900, Brazil.

Pharmaceutical Science Post-Graduation Program, Health Science Institute, Federal University of Pará/UFPA, Belém, PA, 66075900, Brazil.

出版信息

Adv Exp Med Biol. 2017;998:101-112. doi: 10.1007/978-981-10-4397-0_7.

Abstract

Sepsis is one of the main causes of ICU hospitalization worldwide, with a high mortality rate, and is associated with a large number of comorbidities. One of the main comorbidities associated with sepsis is septic cardiomyopathy. This process occurs mainly due to mechanisms of damage in the cardiovascular system that will lead to changes in cardiovascular physiology, such as decreased Ca response, mitochondrial dysfunction and decreased β-adrenergic receptor response. Within this process the exosomes play an important role in the pathophysiology of this disease, in which the exosomal content is related to mechanisms that will trigger its development. After platelet activation through ROS exposition, exosomes containing high concentrations of NADPH are released in heart blood vessels, those exosomes will be internalized in endothelial cells leading to cell death and cardiac dysfunction. On the opposite, exosomes derived from mesenchymal stem cells contain miR-223, that have anti-inflammatory properties, are released in less quantities in septic patients causing an imbalance that leads to cardiac dysfunction.

摘要

脓毒症是全球重症监护病房(ICU)住院的主要原因之一,死亡率很高,且与大量合并症相关。与脓毒症相关的主要合并症之一是脓毒症性心肌病。这个过程主要是由于心血管系统的损伤机制导致的,这些机制会引起心血管生理变化,如钙反应降低、线粒体功能障碍和β-肾上腺素能受体反应降低。在这个过程中,外泌体在这种疾病的病理生理学中起着重要作用,其中外泌体的内容物与引发疾病发展的机制有关。通过活性氧(ROS)暴露激活血小板后,含有高浓度烟酰胺腺嘌呤二核苷酸磷酸(NADPH)的外泌体在心脏血管中释放,这些外泌体将被内皮细胞内化,导致细胞死亡和心脏功能障碍。相反,间充质干细胞衍生的外泌体含有具有抗炎特性的微小核糖核酸-223(miR-223),脓毒症患者释放的此类外泌体数量较少,导致失衡,进而导致心脏功能障碍。

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