Thorac Cardiovasc Surg 2014; 62 - SC24
DOI: 10.1055/s-0034-1367285

Activation of endocannabinoid system is associated with persistent inflammation in human aortic aneurysm

C. Gestrich 1, G.D. Dürr 1, J. Heinemann 1, A. Meertz 1, C. Probst 1, W. Röll 1, A. Zimmer 2, L. Bindila 3, B. Lutz 3, A. Welz 1, O. Dewald 1
  • 1University Clinical Centre Bonn, Dept. of Cardiac Surgery, Bonn, Germany
  • 2Institute for Molecular Psychiatry, Life&Brain, Bonn, Germany
  • 3Institute of Physiological Chemistry, University Medical Centre Mainz, Mainz, Germany

Objectives: Inflammation has been suggested in human aortic aneurysms and associated with remodeling of the vessel wall. Endogenous cannabinoids and their receptors have been shown to modulate inflammatory response and tissue remodeling in many organs. Therefore, we investigated components of the endocannabinoid system, inflammation and remodeling in human aortic aneurysms.

Methods: Specimen of the anterior aortic wall were collected from patients undergoing elective surgery for aortic aneurysm (n = 21) or for coronary artery disease as controls (n = 67). Small buttons of aortic tissue from bypass patients were pooled for molecular analysis and mass spectrometry (n = 21-23). Histological and molecular analyses (qRT-PCR) were performed and endocannabinoids and their metabolites were measured using mass spectrometry.

Results: Patient characteristics were comparable between the groups except for a higher incidence of arterial hypertension and diabetes in the control group. Histological analysis revealed significantly higher density of newly recruited leukocytes (MAC 387+) and macrophages (CD11b+) in the adventitia of the aneurysms. The molecular analysis showed a proinflammatory environment based on up regulation of TNF-α and M-CSF, without induction of chemokines. mRNA-expression of endocannabinoid receptors CB1 and CB2 was significantly higher in aneurysmal tissue than in controls. Concentration of endocannabinoids 1- and 2-arachinoylglycerol was significantly higher, while concentration of anandamide and its metabolites arachidonic acid and palmitoylethanolamide were significantly lower in aortic aneurysm tissue. We further investigated remodeling parameters and found significantly less mRNA-expression of osteopontin, CTGF and MMP-2 in aneurysmal tissue. The collagen stained area was comparable between the aneurysms and control samples.

Conclusions: Our data provide evidence for differential regulation of endocannabinoids, their metabolites and receptors being associated with a persistent low level inflammation and vessel wall remodeling in human aortic aneurysm tissue.