title: Activation of Endocannabinoid System Is Associated with Persistent Inflammation in Human Aortic Aneurysm.
abstract: Human aortic aneurysms have been associated with inflammation and vascular remodeling. Since the endocannabinoid system modulates inflammation and tissue remodeling, we investigated its components in human aortic aneurysms. We obtained anterior aortic wall samples from patients undergoing elective surgery for aortic aneurysm or coronary artery disease as controls. Histological and molecular analysis (RT-qPCR) was performed, and endocannabinoid concentration was determined using LC-MRM. Patient characteristics were comparable between the groups except for a higher incidence of arterial hypertension and diabetes in the control group. mRNA level of cannabinoid receptors was significantly higher in aneurysms than in controls. Concentration of the endocannabinoid 2-arachidonoylglycerol was significantly higher, while the second endocannabinoid anandamide and its metabolite arachidonic acid and palmitoylethanolamide were significantly lower in aneurysms. Histology revealed persistent infiltration of newly recruited leukocytes and significantly higher mononuclear cell density in adventitia of the aneurysms. Proinflammatory environment in aneurysms was shown by significant upregulation of M-CSF and PPARγ but associated with downregulation of chemokines. We found comparable collagen-stained area between the groups, significantly decreased mRNA level of CTGF, osteopontin-1, and MMP-2, and increased TIMP-4 expression in aneurysms. Our data provides evidence for endocannabinoid system activation in human aortic aneurysms, associated with persistent low-level inflammation and vascular remodeling.
authors.affiliation: Department of Cardiac Surgery, University Clinical Centre Bonn, Sigmund-Freud Street 25, 53105 Bonn, Germany.
authors.forename: Christopher
authors.initials: C
authors.lastname: Gestrich
authors.affiliation: Department of Cardiac Surgery, University Clinical Centre Bonn, Sigmund-Freud Street 25, 53105 Bonn, Germany.
authors.forename: Georg D
authors.initials: GD
authors.lastname: Duerr
authors.affiliation: Department of Cardiac Surgery, University Clinical Centre Bonn, Sigmund-Freud Street 25, 53105 Bonn, Germany.
authors.forename: Jan C
authors.initials: JC
authors.lastname: Heinemann
authors.affiliation: Department of Cardiac Surgery, University Clinical Centre Bonn, Sigmund-Freud Street 25, 53105 Bonn, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Meertz
authors.affiliation: Department of Cardiac Surgery, University Clinical Centre Bonn, Sigmund-Freud Street 25, 53105 Bonn, Germany.
authors.forename: Chris
authors.initials: C
authors.lastname: Probst
authors.affiliation: Department of Cardiac Surgery, University Clinical Centre Bonn, Sigmund-Freud Street 25, 53105 Bonn, Germany.
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Roell
authors.affiliation: Department of Cardiac Surgery, University Clinical Centre Bonn, Sigmund-Freud Street 25, 53105 Bonn, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schiller
authors.affiliation: Institute of Molecular Psychiatry, Life & Brain Center, Sigmund-Freud Street 25, 53105 Bonn, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Zimmer
authors.affiliation: Institute of Physiological Chemistry, University Medical Centre of the Johannes Gutenberg University Mainz, Duesbergweg 6, 55128 Mainz, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Bindila
authors.affiliation: Institute of Physiological Chemistry, University Medical Centre of the Johannes Gutenberg University Mainz, Duesbergweg 6, 55128 Mainz, Germany.
authors.forename: Beat
authors.initials: B
authors.lastname: Lutz
authors.affiliation: Department of Cardiac Surgery, University Clinical Centre Bonn, Sigmund-Freud Street 25, 53105 Bonn, Germany.
authors.forename: Armin
authors.initials: A
authors.lastname: Welz
authors.affiliation: Department of Cardiac Surgery, University Clinical Centre Bonn, Sigmund-Freud Street 25, 53105 Bonn, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Dewald
mesh_terms: D000368:Aged; D001011:Aorta / Q000473:pathology; D001014:Aortic Aneurysm / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D055513:Connective Tissue Growth Factor / Q000096:biosynthesis / Q000235:genetics; D003324:Coronary Artery Disease / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D063388:Endocannabinoids / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000235:genetics; D053495:Osteopontin / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis / Q000235:genetics
chemical_list: C526317:CCN2 protein, human; D063388:Endocannabinoids; D012333:RNA, Messenger; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D053495:Osteopontin; D055513:Connective Tissue Growth Factor; D020778:Matrix Metalloproteinase 2