Short summary

With this project we want to determine the relative contribution of and interplay between the endothelial cells, smooth muscle cells, and perivascular adipose tissue of mesenteric resistance arteries to the diminished perfusion of the diseased intestine in Crohn's Disease patients and the contribution hereof to systemic increased inflammation and increased cardiovascular risk in a patient group otherwise displaying a low prevalence of cardiovascular risk factors.

Rationale

Crohn's disease is a chronic inflammatory bowel disease targeting the gastrointestinal tract. In Denmark, the prevalence is 100-200 pr 100.000 citizens. Pharmacological or biological treatment is ineffective, at best prolongs the time from diagnosis to first time intestinal resection. The cause of the disease is unknown; however, a combination of genetic, immunologic, and environmental factors is believed to affect onset and disease progression. The clinical manifestations and symptoms of CD includes chronic diarrhea, abdominal pain, weight loss and blood and/or mucus present in the stool. These symptoms are results of an uncontrolled immune response causing intestinal lesions. Besides the intestinal complications for which surgical resection remains the only option of treatment, 21 - 47 % of CD patients present systemic, extraintestinal manifestations having a strong impact of the patients' quality of life. These manifestations include peripheral arthritis and a higher risk of developing atherosclerosis and related CVDs. Medical treatment includes anti-inflammatory drugs (immunosuppressants and corticosteroids) and biological therapy (antibodies against tumor necrosis factor alpha and integrins) among others. Patients diagnosed with CD have shown a low prevalence of the classical cardiovascular risk factors, but nevertheless an excess risk of cardiovascular events. Especially during periods of relapse, the risk of acute arterial events is increased for patients diagnosed with inflammatory bowel disease (IBD), including CD patients, even at a young age. The severe chronic inflammation is a proposed putative cause, and the oxidative stress observed could serve as a perpetuating factor through immunoregulation. During the state of chronic stress in the attacked site of the intestine an increase in production of reactive oxygen and nitrosative species occur, which leads to oxidative stress and an inhibition of the antioxidant system. The inflammatory response, in here the release of inflammatory cytokines, is proposed to contribute to vascular endothelial dysfunction, and hence increase the cardiovascular burden of CD patients. We aim to decipher the link between the on the one side increased prevalence of CV events and on the other side a lower prevalence of the classical risk factors for CVD, in CD patients. Research focusing on the local events in the intestine affecting local small vessel physiology, function and structure and the cross talk between the diseased tissue and the rest of the body will help understanding the link between oxidative stress, chronic inflammation, and high prevalence of cardiovascular events in CD patients.

Description of the cohort

For the pilot study we want to include 20 patients. Inclusion criteria: patients in need for elective surgery for Crohns disease (10 patients) and patients enrolled for elective right sided hemicolectomy for bowel cancer (10 controls). Both patient groups are recruited from Department of abdominal surgeries (A), Odense University Hospital, the control group from the surgical department with physical location in Svendborg.

Data and biological material

Clinical materials (plasma, biopsies of adipose tissue from healthy and diseased intestine (CD), healthy intestine only (ctrl group), and subcutaneous adipose tissue (both groups). Electronic data (patient demographics, diagnosis, comorbidities, medical treatment).

Collaborating researchers and departments

Dept. Abdominal Surgery (A), OUH

• Mark Bremholm Ellebæk (Head of Research), Niels Qvist (Professor), Thomas Bjørsum-Meyer (Associate professor), Tina Dahl (Research secretary), Betina Møller (project nurse)

University of Southern Denmark, Institute of Molecular Medicine, Department of Cardiovascular and Renal Research

• Maria Bloksgaard (Associate professor)