Maggie Folkesson1, Emina Vorkapic1, Erich Gulbins2, Lukasz Japtok3, Burkhard Kleuser3, Martin Welander4, Toste Länne4, Dick Wågsäter5. 1. Division of Drug Research, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden. 2. Department of Molecular Biology, University of Duisburg-Essen, Essen, Germany; Department of Surgery, University of Cincinnati, Cincinnati, Ohio. 3. Department of Toxicology, Institute of Nutritional Science, University of Potsdam, Potsdam, Germany. 4. Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Faculty of Health Sciences, Linköping University, Linköping, Sweden; Department of Cardiovascular Surgery, County Council of Östergötland, Linköping, Sweden. 5. Division of Drug Research, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden. Electronic address: dick.wagsater@liu.se.
Abstract
BACKGROUND: Abdominal 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 RESULTS: Human 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. CONCLUSIONS: Our results suggest a role for abnormal necrotic, inflamed, proteolytic adipose tissue to the adjacent aneurysmal aortic wall in ongoing vascular damage.
BACKGROUND:Abdominal 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 RESULTS:Human 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. CONCLUSIONS: Our results suggest a role for abnormal necrotic, inflamed, proteolytic adipose tissue to the adjacent aneurysmal aortic wall in ongoing vascular damage.
Authors: Agnieszka Sagan; Tomasz P Mikolajczyk; Wojciech Mrowiecki; Neil MacRitchie; Kevin Daly; Alan Meldrum; Serena Migliarino; Christian Delles; Karol Urbanski; Grzegorz Filip; Boguslaw Kapelak; Pasquale Maffia; Rhian Touyz; Tomasz J Guzik Journal: Front Immunol Date: 2019-09-04 Impact factor: 7.561