环状 RNA UBAP2（hsa_circ_0007367）与微循环灌注相关，可预测行体外膜肺氧合支持的心源性休克患者的结局。

Circular RNA UBAP2 (hsa_circ_0007367) Correlates with Microcirculatory Perfusion and Predicts Outcomes of Cardiogenic Shock Patients Undergoing Extracorporeal Membrane Oxygenation Support.

机构信息

Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Zhejiang Chinese Medical University, Hangzhou, China.

出版信息

Shock. 2022 Jun 1;57(6):200-210. doi: 10.1097/SHK.0000000000001937.

DOI:10.1097/SHK.0000000000001937

PMID:35759302

Abstract

BACKGROUND

Severe microcirculatory disturbance is common in patients with cardiogenic shock necessitating extracorporeal membrane oxygenation (ECMO), however, biomarkers linked to microcirculation and clinical outcome are scarce. Herein we identified a circular RNA, hsa_circ_0007367, rooted from the ubiquitin-associated protein 2 (UBAP2) gene, namely circUBAP2, and evaluated its biological function and the associations with microcirculation and the prognosis.

METHODS

Patients on ECMO with cardiogenic shock were included if qualified sublingual microcirculation parameters could be obtained and were categorized into the survivor group or non-survivor group. Macro-circulatory, microcirculatory data, cytokine levels, and relative circUBAP2 expressions were collected before, at 24 h, and at ECMO weaning off, respectively. The effects of circUBAP2 on the migration, polarization, cytokine productions, and inflammatory pathways in macrophage NR8383 cells were investigated using in vitro methods.

RESULTS

Thirty-three patients with an average age of 58.0 years were enrolled, including 19 survivors and 14 non-survivors. The survivors had higher small vessel density, perfused small vessel density (PSVD), and microvascular flow index (MFI) throughout the ECMO course than did the non-survivors. Relative expression of circUBAP2 (hsa_circ_0007367) correlated with the microcirculatory parameters and satisfactorily predicted the 30-day in-hospital mortality. A multivariable logistic model was developed, showing following four predictors: age (odds ratio [OR] 1.06, 95% confidence interval [CI] 1.00-1.12), time from shock to ECMO (OR 1.10, 95% CI 1.01-1.20), PVSD (OR 0.14, 95% CI 0.02-0.89), and the circUBAP2 expression (OR 0.25, 95% CI 0.08-0.78). In addition, circUBAP2 inhibited the migratory activity and promoted M2 polarization in macrophages, declining the productions of cytokines (tumor necrosis factor [TNF]-α, interleukin [IL]-1β, and monocyte chemotactic protein [MCP]-1) and the PI3K/Akt/mTOR pathway.

CONCLUSION

The expression of circUBAP2 correlates with microcirculatory perfusion and has the potential in predicting outcomes for on-ECMO patients with cardiogenic shock.

摘要

背景

严重的微循环障碍在需要体外膜肺氧合（ECMO）的心源性休克患者中很常见，但是与微循环和临床结果相关的生物标志物却很少。在此，我们鉴定了一种环状 RNA，hsa_circ_0007367，来源于泛素相关蛋白 2（UBAP2）基因，即 circUBAP2，并评估了其生物学功能及其与微循环和预后的关联。

方法

纳入了符合条件的舌下微循环参数可获得且可分为存活组或非存活组的 ECMO 伴心源性休克的患者。分别在 ECMO 前、24 小时和脱机时收集宏观循环、微循环数据、细胞因子水平和相对 circUBAP2 表达。使用体外方法研究 circUBAP2 对巨噬细胞 NR8383 细胞迁移、极化、细胞因子产生和炎症途径的影响。

结果

共纳入 33 例平均年龄为 58.0 岁的患者，其中 19 例存活，14 例死亡。与非存活组相比，存活组在整个 ECMO 过程中小血管密度、灌注小血管密度（PSVD）和微血管血流指数（MFI）更高。环状 RNAUBAP2（hsa_circ_0007367）的相对表达与微循环参数相关，并能很好地预测 30 天院内死亡率。建立了多变量逻辑模型，显示以下四个预测因素：年龄（比值比[OR] 1.06，95%置信区间[CI] 1.00-1.12）、休克到 ECMO 的时间（OR 1.10，95% CI 1.01-1.20）、PSVD（OR 0.14，95% CI 0.02-0.89）和 circUBAP2 表达（OR 0.25，95% CI 0.08-0.78）。此外，circUBAP2 抑制了巨噬细胞的迁移活性并促进了 M2 极化，降低了细胞因子（肿瘤坏死因子[TNF]-α、白细胞介素[IL]-1β和单核细胞趋化蛋白[MCP]-1）和 PI3K/Akt/mTOR 通路的产生。