Inflammatory cells, ceramides, and expression of proteases in perivascular adipose tissue adjacent to human abdominal aortic aneurysms
Autor: | Dick Wågsäter, Emina Vorkapic, Martin Welander, Burkhard Kleuser, Maggie Folkesson, Lukasz Japtok, Erich Gulbins, Toste Länne |
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Jazyk: | angličtina |
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Pathology Necrosis Neutrophils T-Lymphocytes Medizin Adipose tissue 030204 cardiovascular system & hematology Distension environment and public health Pathogenesis Aortic aneurysm 0302 clinical medicine Adipocytes Cardiac and Cardiovascular Systems Mast Cells Kardiologi Cell adhesion molecule Anatomy Abdominal aortic aneurysm Adipose Tissue cardiovascular system Cytokines medicine.symptom Cardiology and Cardiovascular Medicine medicine.medical_specialty Proteases macromolecular substances Ceramides GPI-Linked Proteins Gene Expression Regulation Enzymologic 03 medical and health sciences Antigens CD ddc:570 medicine Humans cardiovascular diseases business.industry Kirurgi Macrophages medicine.disease enzymes and coenzymes (carbohydrates) 030104 developmental biology Surgery Institut für Ernährungswissenschaft business Cell Adhesion Molecules Aortic Aneurysm Abdominal Peptide Hydrolases |
Popis: | BackgroundAbdominal aortic aneurysm (AAA) is a deadly irreversible weakening and distension of the abdominal aortic wall. The pathogenesis of AAA remains poorly understood. Investigation into the physical and molecular characteristics of perivascular adipose tissue (PVAT) adjacent to AAA has not been done before and is the purpose of this study.Methods and ResultsHuman aortae, periaortic PVAT, and fat surrounding peripheral arteries were collected from patients undergoing elective surgical repair of AAA. Control aortas were obtained from recently deceased healthy organ donors with no known arterial disease. Aorta and PVAT was found in AAA to larger extent compared with control aortas. Immunohistochemistry revealed neutrophils, macrophages, mast cells, and T-cells surrounding necrotic adipocytes. Gene expression analysis showed that neutrophils, mast cells, and T-cells were found to be increased in PVAT compared with AAA as well as cathepsin K and S. The concentration of ceramides in PVAT was determined using mass spectrometry and correlated with content of T-cells in the PVAT.ConclusionsOur results suggest a role for abnormal necrotic, inflamed, proteolytic adipose tissue to the adjacent aneurysmal aortic wall in ongoing vascular damage.Clinical RelevanceAbdominal aortic aneurysm is an inflammatory disease. This study shows that adipocytes surrounding the aorta may be a great source of inflammatory leukocytes that are attracted by adipocytes undergoing necrosis and by proinflammatory ceramides. Future strategies preventing the formation of perivascular adipose tissue and targeting inflammation from the adventitial side must be taken into consideration. |
Databáze: | OpenAIRE |
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