Short summary

Odense Artery Biobank - "Relationships between molecular, structural and functional changes in the arterial system and the surrounding perivascular adipose tissue and specific risk factors in cardiovascular surgical patients"

More than every fourth death in Denmark is due to arterial disease and in many of the developing countries arterial disease is a growing problem.

Smoking, inactivity, and obesity are lifestyle factors significantly increasing the risk of developing insulin resistance, diabetes, hyperlipidemia, and hypertension - factors that are all strongly correlated with arterial disease.   

We hypothesize that risk factors such as smoking and diabetes causes subclinical molecular, structural and functional alterations in the arterial system that are present at a very early stage and which eventually leads to vascular stiffness, dysfunctional remodeling, calcification, atherosclerosis and aneurysms, i.e.  a diseased arterial system.

Using modern high-quality techniques for RNA and protein quantitation as well as biomechanical and vasoactive functional testing, we expect to identify some of these very early subclinical changes believed to underlie arterial disease.  

Rationale

Our aim is to establish a human artery biobank by collecting well-defined dissected human arterial tissue samples, gathered from all cardiovascular surgery patients at Odense University Hospital.

A systematic approach, collecting all available tissue will enable us to obtain a large number of high-quality arterial samples allowing us to perform studies with more solid statistical power and to initiate new projects at more integrated levels than traditionally employed on human vascular material.

The arterial biobank is a unique resource for vascular research to be used both for explorative-based data-generated approaches and for hypothesis-driven projects primarily with the aim to define factors and pathways for the pathogenesis of cardiovascular conditions.

Description of the cohort

Patients are included by electively going through cardiovascular surgery - including aortic/mitral valve replacement, maze surgery, coronary artery bypass grafting (CABG), carotid endarterectomy (CEA), thoracic and abdominal aortic aneurysms (TAA and AAA) - at the Department of Cardiac, Thoracic and Vascular Surgery, Odense University Hospital and The Department of Vascular Surgery, Lillebaelt Hospital, Kolding. All participants are over 18 years of age and have given written consent based on oral and written information. 

Data and biological material

Biological material (collected in a systematic and standardized manner)

• Preoperative blood samples (serum and EDTA-plasma).
• Biopsies of parietal pericardium and pericardial fluid.
• Arterial tissue (snap frozen, formalin-fixed paraffin-embedded (FFPE), and cryo-embedded in O.C.T) including left internal mammary artery (LIMA), aortic punch (from aortocoronary bypass), carotid atherectomies, thoracic aortic aneurysm, and abdominal aortic aneurysm (wall and thrombus).
• Adipose tissue including thoracic and abdominal subcutaneous adipose tissue, perivascular adipose tissue (PVAT; from LIMA), epicardial adipose tissue, and peri-aortic root adipose tissue.

Clinical data

• Information regarding smoking habits, BMI, blood pressure/hypertension, lipid profile, diabetes, and use of medicine are registered from patient files and questionnaires.

Collaborating researchers and departments

Department of Clinical Biochemistry and Pharmacology, Odense University Hospital

• Professor Lars Melholt Rasmussen, MD, DMsc

Department of Cardiac, Thoracic and Vascular Surgery, Odense University Hospital

• Professor Jes Sanddal Lindholt, MD, DMSc
• Akhmadjon Irmukhamedov, MD
• Lars Peter Riber, MD, PhD

Department of Cardiology, Odense University Hospital

• Associate professor Axel Diederichsen, MD, PhD
• Professor Jacob Eifer Møller, MD, DMSc

Department of Vascular Surgery. Lillebaelt Hospital, Kolding

• Professor Kim Christian Houlind, MD, PhD

Department of Molecular Medicine, University of Southern Denmark

• Professor Jo de Mey, PhD
• Associate professor Maria Bloksgaard, PhD
• Associate professor Jane Stubbe, PhD

Publications associated with the project

Imaging and modeling of acute pressure-induced changes of collagen and elastin microarchitectures in pig and human resistance arteries. Bloksgaard M, Leurgans TM, Spronck B, Heusinkveld MHG, Thorsted B, Rosenstand K, Nissen I, Hansen UM, Brewer JR, Bagatolli LA, Rasmussen LM, Irmukhamedov A, Reesink KD, De Mey J. Am J Physiol Heart Circ Physiol. 2017 Jul 1;313(1):H164-H178. doi: 10.1152/ajpheart.00110.2017. Epub 2017 Apr 21.

The water channel AQP1 is expressed in human atherosclerotic vascular lesions and AQP1 deficiency augments angiotensin II-induced atherosclerosis in mice. Wintmo P, Johansen SH, Hansen PB, Lindholt JS, Urbonavicius S, Rasmussen LM, Bie P, Jensen BL, Stubbe J. Acta Physiol (Oxf). 2017 Jan 27. doi: 10.1111/apha.12853. [Epub ahead of print]

Arterial Iron Content Is Increased in Patients with High Plasma Ferritin Levels. Madsen JB, Pedersen L, Kidholm CL, Rasmussen LM. J Vasc Res. 2016;53(5-6):301-307. doi: 10.1159/000452799. Epub 2016 Dec 10.

SHP-1 activation inhibits vascular smooth muscle cell proliferation and intimal hyperplasia in a rodent model of insulin resistance and diabetes. Qi W, Li Q, Liew CW, Rask-Madsen C, Lockhart SM, Rasmussen LM, Xia Y, Wang X, Khamaisi M, Croce K, King GL.

Insulin Downregulates the Transcriptional Coregulator CITED2, an Inhibitor of Proangiogenic Function in Endothelial Cells. Wang X, Lockhart SM, Rathjen T, Albadawi H, Sørensen D, O'Neill BT, Dwivedi N, Preil SR, Beck HC, Dunwoodie SL, Watkins MT, Rasmussen LM, Rask-Madsen C. Diabetes. 2016 Dec;65(12):3680-3690. Epub 2016 Aug 25.

P/Q-type and T-type voltage-gated calcium channels are involved in the contraction of mammary and brain blood vessels from hypertensive patients. Thuesen AD, Lyngsø KS, Rasmussen L, Stubbe J, Skøtt O, Poulsen FR, Pedersen CB, Rasmussen LM, Hansen PB. Acta Physiol (Oxf). 2017 Mar;219(3):640-651. doi: 10.1111/apha.12732. Epub 2016 Jun 29.

Insulin decreases atherosclerosis by inducing endothelin receptor B expression. Park K, Mima A, Li Q, Rask-Madsen C, He P, Mizutani K, Katagiri S, Maeda Y, Wu IH, Khamaisi M, Preil SR, Maddaloni E, Sørensen D, Rasmussen LM, Huang PL, King GL. JCI Insight. 2016 May 5;1(6). pii: e86574.

Adipokine Imbalance in the Pericardial Cavity of Cardiac and Vascular Disease Patients. Elie AG, Jensen PS, Nissen KD, Geraets IM, Xu A, Song E, Hansen ML, Irmukhamedov A, Ras-mussen LM, Wang Y, De Mey JG. PLoS One. 2016 May 3;11(5):e0154693. doi: 10.1371/journal.pone.0154693. eCollection 2016.

Smoking is associated with lower amounts of arterial type I collagen and decorin. Faarvang AS, Rørdam Preil SA, Nielsen PS, Beck HC, Kristensen LP, Rasmussen LM. Atherosclerosis. 2016 Apr;247:201-6. doi: 10.1016/j.atherosclerosis.2016.02.022. Epub 2016 Feb 21.

Endothelin-1 shifts the mediator of bradykinin-induced relaxation from NO to H2 O2 in resistance arteries from patients with cardiovascular disease. Leurgans TM, Bloksgaard M, Brewer JR, Bagatolli LA, Fredgart MH, Rosenstand K, Hansen ML, Rasmussen LM, Irmukhamedov A, De Mey JG.Br J Pharmacol. 2016 May;173(10):1653-64. doi: 10.1111/bph.13467. Epub 2016 Apr 6.