Gene expression alterations induced by low molecular weight heparin during bowel anastomosis healing in rats

• Authors: Natalia Krześniak , Agnieszka Paziewska , Tymon Rubel , Magdalena Skrzypczak , Michał Mikula , Artur Dzwonek , Krzysztof Goryca , Lucjan S. Wyrwicz , Dorota Jarosz , Daniel Laubitz , Marek Woszczyński , Krzysztof Bielecki , Jerzy Ostrowski
• Languages of publication: EN

Abstracts

EN

Colon anastomosis is therapeutically challenging because multiple, usually undetectable factors influence a spectrum of repair mechanisms. We hypothesized that low molecular weight heparins, routinely administered perioperatively, may differentially affect gene expression related to colon healing. Twenty pairs of untreated and enoxaparin-treated rats underwent left-side hemicolectomy with a primary end-to-end anastomosis. Normal colon and anastomotic bowel segments were resected on day 0 and on days 1, 3, 5, and 7 after surgery, respectively. Serial anastomosis transverse cross-sections were evaluated microscopically and by microarray (Rat Genome 230 2.0, Affymetrix). Differentially expressed probe sets were annotated with Gene Ontology. We also examined the influence of enoxaparin on fibroblast proliferation and viability in vitro. Among the 5476 probe sets, we identified differential expression at each healing time point, yielding 79 subcategories. Most indicated genes were involved in wound healing, including multicellular organismal development, locomotory behavior, immune response, cell adhesion, inflammatory response, cell-cell signaling, blood vessel development, and tissue remodeling. Although we found no intensity differences in histological features of healing between enoxaparin-treated and control rats, treatment did induce significant expression changes during early healing. Of these changes, 83 probe sets exhibited at least twofold changes and represented different functional annotations, including inflammatory response, regulation of transcription, regulation of apoptosis, and angiogenesis. Fibroblast culture confirmed an anti-viability effect of enoxaparin. Enoxaparin affects colon wound-related gene expression profiles, but further studies will resolve whether heparin treatment is a risk factor after intestinal surgery, at least in some patients.

Keywords

EN

heparins; gene expression; wound healing; microarrays

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2011
• Volume: 58
• Issue: 1
• Pages: 79-87

Dates

published

2011

received

2010-08-16

revised

2010-12-28

accepted

2011-01-21

(unknown)

2011-03-18

Contributors

author

Natalia Krześniak

• Department of General and Gastrointestinal Tract Surgery, Medical Center for Postgraduate Education, Warszawa, Poland

author

Agnieszka Paziewska

• Department of Gastroenterology and Hepatology, Medical Center for Postgraduate Education, Warszawa, Poland

author

Tymon Rubel

• Laboratory of Bioinformatics and Systems Biology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warszawa, Poland

author

Magdalena Skrzypczak

• Department of Gastroenterology and Hepatology, Medical Center for Postgraduate Education, Warszawa, Poland

author

Michał Mikula

• Department of Gastroenterology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warszawa, Poland

author

Artur Dzwonek

• Department of Gastroenterology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warszawa, Poland

author

Krzysztof Goryca

• Department of Gastroenterology and Hepatology, Medical Center for Postgraduate Education, Warszawa, Poland

author

Lucjan S. Wyrwicz

• Laboratory of Bioinformatics and Systems Biology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warszawa, Poland

author

Dorota Jarosz

• Department of Gastroenterology and Hepatology, Medical Center for Postgraduate Education, Warszawa, Poland

author

Daniel Laubitz

• The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, Warszawa, Poland

author

Marek Woszczyński

• Department of Animal Genetics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warszawa, Poland

author

Krzysztof Bielecki

• Department of General and Gastrointestinal Tract Surgery, Medical Center for Postgraduate Education, Warszawa, Poland

author

Jerzy Ostrowski

• Department of Gastroenterology and Hepatology, Medical Center for Postgraduate Education, Warszawa, Poland

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