Proteomics Reveals Urine Apolipoprotein A-I As A Potential Biomarker Of Acute Kidney Injury Following Percutaneous Coronary Intervention In Elderly Patients

EXPERIMENTAL AND THERAPEUTIC MEDICINE(2021)

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摘要
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.
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关键词
percutaneous coronary intervention, acute kidney injury, proteomics, apolipoprotein A-I, biomarker
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