Zhou Fangfang, Luo Qun, Han Lina, Shen Gen, Huang Lulu, Ye Honghua
Department of Nephrology, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang 315010, P.R. China.
Department of Cardiology, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang 315010, P.R. China.
Exp Ther Med. 2021 Jul;22(1):745. doi: 10.3892/etm.2021.10177. Epub 2021 May 11.
The aim of the present study was to investigate how changes in the lipid composition are involved in early stages of acute kidney injury (AKI) following percutaneous coronary intervention (PCI-AKI) in elderly patients. A prospective nested case-control study was performed. Alterations in the urine protein accumulation were investigated in patients with and without PCI-AKI using isobaric tags for relative and absolute quantitation (iTRAQ). In addition, differentially expressed proteins (DEPs) related to lipids were confirmed using parallel reaction monitoring (PRM)-based targeted proteomics. From the cohort of elderly patients (>60 years of age), 14 (12.28%) developed AKI within 48 h after PCI. No significant differences were detected between the AKI and control (CON) groups for serum creatinine at 24 h following treatment (P=0.27). Among the DEPs that overlapped in both the AKI-24 h/AKI-Pre (AKI group at 24 h post-PCI vs. pre-PCI) and AKI-24 h/CON-24 h groups (AKI group vs. CON group at 24 h post-PCI), only apolipoprotein A-I (apoA-I) was related to lipids, which displayed a significant upregulation in expression levels. The protein expression levels of apoA-I displayed a 5.98-fold increase at 24 h after PCI from the baseline and a 2.09-fold increase compared with the control group as determined using PRM, which exhibited a similar trend to the iTRAQ results. Using protein-protein interaction analyses, apoA-I was determined to be functionally linked to the complement and coagulation cascades, the renin-angiotensin system and the hypoxia-inducible factor-1 signaling pathway. Using the pathway analysis tool from the Kyoto Encyclopedia of Genes and Genomes, several pathways were identified to be associated with apoA-I, including fat digestion and absorption, vitamin digestion and absorption, as well as the peroxisome proliferator activated receptor signaling pathway. In conclusion, apoA-I may be a promising biomarker for the early diagnosis of PCI-AKI in elderly patients. The role of apoA-I in the pathobiology of PCI-AKI requires further exploration.
本研究的目的是调查脂质成分变化如何参与老年患者经皮冠状动脉介入治疗后急性肾损伤（PCI-AKI）的早期阶段。进行了一项前瞻性巢式病例对照研究。使用等压标签相对和绝对定量（iTRAQ）研究了有和没有PCI-AKI的患者尿蛋白积累的变化。此外，使用基于平行反应监测（PRM）的靶向蛋白质组学确认了与脂质相关的差异表达蛋白（DEP）。在老年患者（>60岁）队列中，14例（12.28%）在PCI后48小时内发生AKI。治疗后24小时，AKI组和对照组（CON）的血清肌酐无显著差异（P=0.27）。在AKI-24小时/AKI-术前（PCI术后24小时的AKI组与PCI术前）和AKI-24小时/CON-24小时组（PCI术后24小时的AKI组与CON组）中重叠的DEP中，只有载脂蛋白A-I（apoA-I）与脂质相关，其表达水平显著上调。使用PRM测定，PCI后24小时apoA-I的蛋白表达水平相对于基线增加了5.98倍，与对照组相比增加了2.09倍，这与iTRAQ结果显示出相似的趋势。通过蛋白质-蛋白质相互作用分析，确定apoA-I在功能上与补体和凝血级联、肾素-血管紧张素系统以及缺氧诱导因子-1信号通路相关。使用京都基因与基因组百科全书的通路分析工具，确定了几条与apoA-I相关的通路，包括脂肪消化和吸收、维生素消化和吸收以及过氧化物酶体增殖物激活受体信号通路。总之，apoA-I可能是老年患者PCI-AKI早期诊断的有前景的生物标志物。apoA-I在PCI-AKI病理生物学中的作用需要进一步探索。
