miRNA-200b - A potential biomarker identified in a porcine model of cardiogenic shock and mechanical unloading

Cardiogenic 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. Methods: CS 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 minutes 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. Results: CS 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. Conclusions: The 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 minutes 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. Circulating RNA expression profiles of pigs under basal conditions, after the onset of CS, and following additional pVAD unloading.

心源性休克（Cardiogenic shock, CS）可改变全身代谢状态，循环生物标志物可作为心源性休克患者的预后评估指标。经皮心室辅助装置（percutaneous ventricular assist devices, pVADs）通过主动将血液泵入主动脉，实现左心室的卸载减负。本研究旨在通过大型动物模型，鉴定循环代谢物与转录本的变化特征，以期发现可作为急性心源性休克以及联合Impella®经皮心室辅助装置实施额外左心室卸载后的潜在预后生物标志物。

方法：本研究采用6头猪构建临床前大型动物模型，通过向左冠状动脉系统注入微球诱导心源性休克。心源性休克造模完成后，启动经皮心室辅助装置支持，总时长为30分钟。分别在基础状态、心源性休克造模后以及经pVAD实施额外卸载后采集血清样本。采用代谢组学分析检测循环代谢物，通过RNA测序技术分析循环RNA分子。

结果：心源性休克以及额外pVAD支持可改变参与氨酰-tRNA生物合成与氨基酸代谢的循环代谢物的丰度。RNA测序结果显示，心源性休克造模后缺氧敏感型miRNA-200b的丰度降低，而经pVAD支持后该丰度可恢复至原有水平。

结论：缺氧相关microRNA（hypoxamir）miRNA-200b是一种潜在的循环标志物，在心源性休克状态下其表达受到抑制，经pVAD支持后可恢复正常。仅经30分钟pVAD支持后，miRNA-200b的表达即出现上调的早期转录反应，提示机械性心室卸载可改变全身代谢状态。未来仍需开展相关研究，以明确血清miRNA-200b水平作为急性心源性休克患者及接受pVAD卸载治疗患者的预后标志物的临床价值。本数据集包含基础状态下、心源性休克发作后以及经pVAD实施额外卸载后猪的循环RNA表达谱。