Table_4_miRNA-200b—A Potential Biomarker Identified in a Porcine Model of Cardiogenic Shock and Mechanical Unloading.xls

BackgroundCardiogenic shock (CS) alters whole body metabolism and circulating biomarkers serve as prognostic markers in CS patients. Percutaneous ventricular assist devices (pVADs) unload the left ventricle by actively ejecting blood into the aorta. The goal of the present study was to identify alterations in circulating metabolites and transcripts in a large animal model that might serve as potential prognostic biomarkers in acute CS and additional left ventricular unloading by Impella ® pVAD support.MethodsCS was induced in a preclinical large animal model by injecting microspheres into the left coronary artery system in six pigs. After the induction of CS, mechanical pVAD support was implemented for 30 min total. Serum samples were collected under basal conditions, after the onset of CS, and following additional pVAD unloading. Circulating metabolites were determined by metabolomic analysis, circulating RNA entities by RNA sequencing.ResultsCS and additional pVAD support alter the abundance of circulating metabolites involved in Aminoacyl-tRNA biosynthesis and amino acid metabolism. RNA sequencing revealed decreased abundance of the hypoxia sensitive miRNA-200b following the induction of CS, which was reversed following pVAD support.ConclusionThe hypoxamir miRNA-200b is a potential circulating marker that is repressed in CS and is restored following pVAD support. The early transcriptional response with increased miRNA-200b expression following only 30 min of pVAD support suggests that mechanical unloading alters whole body metabolism. Future studies are required to delineate the impact of serum miRNA-200b levels as a prognostic marker in patients with acute CS and pVAD unloading.

背景：心源性休克（CS）会改变全身代谢，循环中的生物标志物在CS患者中充当预后标志。经皮室间隔辅助装置（pVADs）通过主动将血液射入主动脉来卸载左心室。本研究旨在识别在大型动物模型中循环代谢物和转录本的变化，这些变化可能作为急性CS和Impella® pVAD支持额外左心室卸载的潜在预后生物标志物。方法：通过向六头猪的左冠状动脉系统注射微球在预临床大型动物模型中诱导CS。在CS诱导后，实施了总共30分钟的机械pVAD支持。在基础条件下、CS发生时以及额外pVAD卸载后收集血清样本。通过代谢组学分析确定循环代谢物，通过RNA测序确定循环RNA实体。结果：CS和额外pVAD支持改变了参与氨基酸-tRNA生物合成和氨基酸代谢的循环代谢物的丰度。RNA测序显示，在CS诱导后，对缺氧敏感的miRNA-200b的丰度降低，而在pVAD支持后逆转。结论：缺氧微RNA-200b是一种潜在的循环标志物，在CS中被抑制，而在pVAD支持后得到恢复。仅30分钟的pVAD支持后，miRNA-200b表达增加的早期转录反应表明，机械卸载会改变全身代谢。未来的研究需要阐明血清miRNA-200b水平作为急性CS和pVAD卸载患者预后标志物的影响。