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.

The Roles of Matrix Metalloproteinases and Their Inhibitors in Human Diseases

“…TIMP-4 counteracts MMP-2, allowing a balanced matrix turnover to be achieved. The difference in the MMP-2:TIMP-4 ratio reflects this balance in patients with aortic aneurysms [ 272 ]. Low levels of both TIMP-2 and TIMP-1 in aortic aneurysms may represent a favorable environment for aneurysm expansion and collagen degradation [ 273 ].…”