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 PPAR 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.

TRPV1 inhibits smooth muscle cell phenotype switching in a mouse model of abdominal aortic aneurysm

“…These results suggested that TRPV1 has a protective effect in cardiovascular diseases. Although one study demonstrated that TRPV1 expression was increased in patients with ascending aortic aneurysm, which seemed to be contradictory with our results [27], it should be noted that the origin of VSMCs in the ascending aorta was different from the abdominal aorta [28]. Nogi M et al reported that disruption and degradation of medial elastic lamina in the ascending aorta were more severe in ApoE −/-SmgGDS ± mice compared with ApoE −/mice after AngII infusion for 4 weeks.…”

Increased Renal 2-Arachidonoylglycerol Level Is Associated with Improved Renal Function in a Mouse Model of Acute Kidney Injury

“…Indeed, there are recent studies that link increased 2-AG levels with worsening of inflammation. 37 , 38 It is possible that increased tissue levels of 2-AG may lead to activation of CB 1 receptor, hence causing a trend toward worsening inflammation; however, this mechanism has not been established in renal IRI. Given that indices of renal inflammation and oxidative stress remain unchanged, our findings support the notion that the modest improvement in renal function observed with enhanced 2-AG levels may be related to effects independent of its role in inflammation and oxidative stress.…”

Anandamide and endocannabinoid system: an attractive therapeutic approach for cardiovascular disease

“…The mentioned data provide evidence on the activation of ECS in human aortic aneurysms associated with chronic inflammation and vascular remodeling. 53 Recent evidence shows there are interactions between the RAAS system and the ECS, suggesting AEA and 2-AG can regulate vascular contraction caused by Ang II, which can occur independently of the CB 1 receptor. This process is of great importance since, for example, increasing vascular sensitivity to Ang II is a marker of eclampsia.…”

“…The mentioned data provide evidence on the activation of ECS in human aortic aneurysms associated with chronic inflammation and vascular remodeling. 53…”