Differential secretion of prostaglandin E2, thromboxane A2 and interleukin-6 in intact and ruptured abdominal aortic aneurysms

Abstract

Ruptured abdominal aortic aneurysm (AAA) contributes largely to aneurysm-related morbidity and mortality. An inflammatory gene, COX-2, was found to be widely expressed in AAA. However, the involvement of COX-2 metabolites and other inflammatory mediators in the disease and particularly in AAA rupture still needs elucidation. The purpose of the present study was to evaluate the secretion of inflammatory mediators and the expression of macrophages in aneurysms and determine their significance in ruptured AAA. Aortic tissue was harvested at time of aortic reconstructive surgery for the group of intact AAA (n=20) and ruptured AAA (n=10) or at time of organ harvest for normal aortic tissue (n=4). Aortic explant cultures were immediately established and the culture medium was collected after 72 h. Specific enzyme-linked immunoassorbent assays were used to quantify COX-2 metabolites and inflammatory cytokines. Inflammatory macrophage cells were also quantified in the corresponding aortic walls immunohistochemically. Differences in the secretory levels of inflammatory metabolites and the macrophage quantity in all groups were assessed. All three explant culture groups secreted detectable levels of studied COX-2 metabolites, including PGE 2 , PGF 2α , PGI 2 and TxB 2 and inflammatory cytokines, including interleukin (IL)-1ß, IL-6, IL-8 and IL-10. The secretory levels of PGE 2 , TXB 2 and IL-6 were highest in the ruptured AAA explant cultures and statistically higher than those in intact AAA cultures (p<0.05). The secretion of those inflammatory mediators and the local expression of macrophages in ruptured aneurysm probably reflects the active inflammatory processes in the aortic lesions. A means of modifying the inflammatory process in the wall of AAAs might play an important role in preventing aneurysm rupture.

Increased 18F-FDG Uptake Is Predictive of Rupture in a Novel Rat Abdominal Aortic Aneurysm Rupture Model

“…44 Morphometric analysis of human tissue has demonstrated significantly greater macrophage populations in ruptured AAA tissue compared with intact AAA tissue. 45 We observed significantly increased macrophage populations in RAAA tissue compared with NRAAA 14d tissue, and this is consistent with a cytokine profile representative, in part, of increased macrophage presence and/or activity. Our observation of decreased macrophage populations in CAAA 14d tissue compared with CAAA 6d tissue is consistent with our earlier work evaluating macrophage infiltration in the PPE-exposed mouse aorta at 7 and 14 days post-PPE exposure.…”

Microvascular COX-2/mPGES-1/EP-4 axis in human abdominal aortic aneurysm

“…Because COX-2 and mPGES-1 were expressed in both, vascular cells and infi ltrating cells, macrophages could also be a relevant source of PGE 2 in the AAA. Indeed, macrophage COX-2-derived PGE 2 has been found to be relevant in the pathogenesis and rupture of AAAs ( 12,13,21,22 ). We cannot rule out, however, the contribution of macrophage-associated COX-1 to the PGE 2 pool, because we found that COX-1 is increased in AAA, probably due to recruited macrophages as mentioned above.…”

“…In these models, AAA develops fast and its etiology differs substantially from human pathology. Despite the role of PGE 2 in neovascularization in cancer and other pathologies, and that the relevance of angiogenesis in AAA is widely accepted, information concerning COX-2/mPGES-1-derived PGE 2 in the AAA, particularly in AAA-associated hypervascularization, is limited and restricted to COX-2-derived PGE 2 from macrophages ( 12,13,21,22 ). Furthermore, the benefi cial effects of COX-2 inhibitors and the deletion of mPGES-1 or EP-4 in experimental AAA are not fully understood in the context of this pathology in humans.…”

Plasma cytokine levels and risks of abdominal aortic aneurysms: A population-based prospective cohort study

“…Most studies suggest an increase of pro-inflammatory cytokines, such as IL6, TNF-α, IL1β, IFN-γ, and IL17A, in either plasma or aortic tissue extracts from AAA patients (18, 20, 21), particularly in those with ruptured AAAs (19, 23). In contrast, AAA patient plasma or explant AAA lesion culture (22, 24) often exhibits lower levels of anti-inflammatory cytokines, such as IL10, particularly in patients with ruptured AAAs (23).…”

“…In contrast, AAA patient plasma or explant AAA lesion culture (22, 24) often exhibits lower levels of anti-inflammatory cytokines, such as IL10, particularly in patients with ruptured AAAs (23). Yet other studies showed that plasma IL6 levels remained stagnant between AAAs and controls, and did not correlate with AAA growth rate (25, 26).…”