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Published on: September 27, 2024
Early Elevation of Cell-Free DNA After Acute Mesenteric Ischemia in Rats
Satoshi Karasawa1, Taka-Aki Nakada1, Mamoru Sato2
1Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine, Chiba 260-8677, Japan.
Background:
Acute mesenteric ischemia (AMI) is challenging to diagnose in the early phase. We tested the hypothesis that blood levels of cell-free DNA would increase early after AMI. In addition, proteome analysis was conducted as an exploratory analysis to identify other potential diagnostic biomarkers.
Methods:
Mesenteric ischemia, abdominal sepsis, and sham model were compared in Sprague-Dawley rats. The abdominal sepsis model was induced by cecum puncture and mesenteric ischemia model by ligation of the superior mesenteric artery. Blood levels of cell-free DNA were measured 2 h and 6 h after wound closure. Shotgun proteome analysis was performed using plasma samples obtained at the 2 h timepoint; quantitative analysis was conducted for proteins detected exclusively in the AMI models.
Results:
Blood cell-free DNA levels at 2 h after wound closure were significantly higher in the AMI model than in the sham and the abdominal sepsis models (P < 0.05). Cell-free DNA was positively correlated with the pathologic ischemia severity score (correlation coefficient 0.793-0.834, P < 0.001). Derivative proteome analysis in blood at 2-h time point revealed higher intensity of paraoxonase-1 in the AMI models than in the abdominal sepsis models; the significantly high blood paraoxonase-1 levels in the AMI models were confirmed in a separate quantitative analysis (P = 0.015).
Conclusions:
Cell-free DNA was demonstrated to be a promising biomarker for the early diagnosis of mesenteric ischemia in a rat model of AMI. Paraoxonase-1 may also play a role in the differential diagnosis of mesenteric ischemia from abdominal sepsis. The current results warrant further investigation in human studies.
Insights
Early diagnosis of acute mesenteric ischemia (AMI) is challenging. Cell-free DNA and paraoxonase-1 show promise as early diagnostic biomarkers in a rat model, aiding differential diagnosis from abdominal sepsis.
Area of Science:
- Biochemistry
- Molecular Biology
- Surgical Research
Background:
- Acute mesenteric ischemia (AMI) presents diagnostic challenges in its early stages.
- Identifying reliable early diagnostic biomarkers for AMI is crucial for timely intervention.
- Proteomic analysis offers potential for discovering novel biomarkers.
Purpose of the Study:
- To investigate the potential of cell-free DNA as an early diagnostic biomarker for AMI.
- To explore proteomic profiles for additional diagnostic markers in AMI.
- To differentiate AMI from abdominal sepsis using molecular markers.
Main Methods:
- Comparison of Sprague-Dawley rat models: AMI (superior mesenteric artery ligation), abdominal sepsis (cecum puncture), and sham.
- Measurement of blood cell-free DNA levels at 2 and 6 hours post-induction.
- Shotgun and quantitative proteome analysis of plasma samples at 2 hours.
Main Results:
- Significantly elevated blood cell-free DNA levels were observed in the AMI model at 2 hours compared to sham and sepsis models (P < 0.05).
- Cell-free DNA levels strongly correlated with ischemia severity (correlation coefficient 0.793-0.834, P < 0.001).
- Elevated paraoxonase-1 levels were detected in AMI models, suggesting a role in differentiating AMI from sepsis (P = 0.015).
Conclusions:
- Cell-free DNA is a promising biomarker for early diagnosis of mesenteric ischemia in an AMI rat model.
- Paraoxonase-1 may aid in the differential diagnosis between mesenteric ischemia and abdominal sepsis.
- Further human studies are warranted to validate these findings.
