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Presenter: Laurens, Ceulemans, Leuven, Belgium
Authors: Laurens Ceulemans, Gert De Hertogh, Ricard Farré, Jean-Paul Decuypere, Len Verbeke, Ina Jochmans, Diethard Monbaliu, Kaatje Lenaerts, Jacques Pirenne
Laurens Ceulemans1, Gert De Hertogh2, Ricard Farré3, Jean-Paul Decuypere1, Len Verbeke3, Ina Jochmans1, Diethard Monbaliu1, Kaatje Lenaerts4, Jacques Pirenne1.
1Abdominal Transplant Surgery, University Hospitals Leuven, KULeuven, Leuven, Belgium; 2Pathology, University Hospitals Leuven, KULeuven, Leuven, Belgium; 3Gastro-enterology, University Hospitals Leuven, KULeuven, Leuven, Belgium; 4Surgery, University of Maastricht, Maastricht, Netherlands
Introduction: Intestinal ischemia remains a frequent pathology with a mortality rate up to 80%, due to delayed diagnosis and lack of efficient therapy. Intestinal reperfusion enhances the catastrophic effect of ischemia, known as ischemia-reperfusion injury (IRI). In contrast to other organs, serological markers for intestinal IRI are missing. We have accumulated evidence that villin-1 -a protein anchoring the actin filaments at the epithelial brush border- is a valuable candidate.
The aim was to analyze villin-1 as a serological biomarker in a rodent and human model of intestinal ischemia reperfusion injury (IRI).
Methods: In a rat model of intestinal IRI (temporary mesenteric artery clamping), 4 conditions were tested: (i) laparotomy only (sham); (ii) 30min ischemia + 5 reperfusion periods (0min/30min/60min/120min/24hours); (iii) 45min ischemia + 5 reperfusion periods; (iv) 60min ischemia + 5 reperfusion periods; (n=6/group). For survival analysis, 7-day reperfusion was included in each condition (n=10/group). Other end-points that were analyzed: histology (Park-Chiu/villus length); intestinal permeability (Ussing chamber); villin-1 (Western-Blot).
In a validated human model of intestinal IRI (6cm jejunal-clamping during pancreaticoduodenectomy; 45min ischemia + 0min/30min/120min reperfusion) villin-1 was analyzed by immunoprecipitation (n=6).
Results: In rat, increasing ischemia resulted in decreased survival (30min: 90%; 45min: 50%; 60min: 10%) and loss of intestinal integrity (histology/permeability). From 45min ischemia, villin-1 appeared in the plasma at 0min reperfusion and remained detectable until 120min reperfusion (Figure 1). At 0min reperfusion, villin-1 could differentiate between 45min or 60min ischemia corresponding to the different survival. Overall, villin-1 had a strong correlation with Park-Chiu score (r=0.7954;p<0.0001); villus length (r=-0.6585;p<0.0001); and permeability (r=-0.6127;p=0.0019).
In human, villin-1 was released with ischemia and remained detectable until 120min reperfusion (Figure 2).
Conclusion: For the first time, we showed that villin-1 is a serological biomarker of intestinal IRI in rat and human. These findings open new perspectives in the diagnosis of intestinal ischemia and warrant further clinical investigations.
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