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
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