Abstract 4965: High Mobility Group Box 1 Protein Expression is Associated With Expansion and Rupture of Human Abdominal Aortic Aneurysm
Background: Abdominal aortic aneurysm (AAA) expansion is characterized by widespread transmural inflammation and extracellular matrix degradation. High mobility group box1 protein (HMGB1) is one of the recently defined damage-associated molecular pattern molecules derived from necrotic and activated inflammatory cells, and functions as a proinflammatory mediator. The aim of this study was to elucidate the clinical significance of HMGB1 expression in patients with AAA.
Methods and Results: Serum HMGB1 concentration was measured by enzyme-linked immunosorbent assay in 40 patients with infrarenal AAA (6 patients with ruptured and 34 patients with nonruptured AAA), who underwent surgical repair of AAA. Serum HMGB1 level on admission did not differ between the presence or absence of atherosclerotic risk factors, including smoking, hypertension, hyperlipidemia, age and sex, and cardiovascular medications. These variables were similar between patients with ruptured and nonruptured AAA. Serum HMGB1 level was significantly higher in patients with ruptured AAA compared with nonruptured AAA (4.9±3.4 vs 1.9±2.9 ng/ml, p<0.05). Thirty-eight AAA tissues taken during surgical repair were examined for immunoblotting (4 ruptured and 34 nonruptured AAA). The HMGB1 level in aneurysmal tissue was positively correlated with AAA diameter (r=0.43, p<0.05). In addition, HMGB1 expression was higher in patients with ruptured AAA than those with nonruptured AAA (p<0.05). Gelatin zymography showed that matrix metalloproteinase (MMP)-2 and -9 levels were significantly elevated in the ruptured AAA compared with nonruptured AAA (all p<0.05). Patients with MMP-2 level>median value had a higher HMGB1 level in aneurysmal tissue than those without (p<0.05). Immunohistochemistry demonstrated that HMGB1 was highly expressed in macrophages and neutrophils within the degenerating aortic media and periadvential fat tissues of AAA. HMGB1 was also expressed in smooth muscle cells and fibroblasts within the degenerating aortic media.
Conclusions: Elevation of HMGB1 level in serum and aneurysmal tissue was observed in patients with expansion and rupture of AAA, in association with activation of MMPs. Serum HMGB1 could be a useful marker of the development of AAA rupture.