Blocking Interleukin-1 Beta Reduces the Evolution of Thoracic Aortic Dissection in a Rodent Model.

OBJECTIVE: Thoracic aortic dissection (TAD) is associated with matrix changes, biochemical changes, and inflammatory markers like interleukin-1 beta (IL-1ß). However, the exact mechanism remains unknown. This study aimed to investigate the role of IL-1ß, matrix metalloproteinase (MMP)-2, MMP-9, smooth muscle cell apoptosis, and elastic fibre fracture in the development of TAD in a rat model. METHODS: The TAD rat model was induced by ß-aminopropionitrile (BAPN). TAD was investigated in 112 male Sprague-Dawley rats, which were equally divided into four groups of 28 rats (Control, BAPN, BAPN + IL-1ß, and BAPN + IL-1ß antibody). Systolic blood pressure, survival, and the development of TAD were measured after six weeks. Expression of IL-1ß, MMP-2, and MMP-9 was measured by Western blot. Apoptosis, aortic elastin concentration, and biomechanical characteristics were measured by the TdT mediated dUTP nick end labelling assay, Victoria blue staining, and in vitro testing. RESULTS: During six weeks, the mortality was 0% (0/28) in the control group, 53.6% (15/28) in the BAPN group (p < .001 compared with the control group), 75.0% (21/28) in the BAPN + IL-1ß group (p = .007 compared with the BAPN group), and 35.7% (10/28) in the BAPN + IL-1ß antibody group (p = .023 compared with BAPN group and p < .001 compared with the BAPN + IL-1ß group). IL-1ß treatment deteriorates BAPN induced mortality and aneurysm expansion, which were attenuated by anti-IL-1ß treatment. In BAPN + IL-1ß group, stress and strain parameters were decreased by 13.5%-53.5% and elastin content was decreased by 14%, and IL-1ß, MMP-2, and MMP-9 were expressed higher by 117%, 108%, and 75% when compared with the rats in the BAPN group. Contrarily, in the BAPN + IL-1ß antibody group, the above changes could be completely (strain, elastin content, and expression of MMP-2) or partly (elasticity modulus, stress, and expression of MMP-9) blocked by anti-IL-1ß treatment. CONCLUSION: IL-1ß plays a critical role in TAD formation by altering the expression of MMP-2 and MMP-9, degrading the aortic wall matrix, causing elastic fibre rupture, and changing the stress or strain of the aortic wall. Anti-IL-1ß reduces the later effects and could be one of the molecular targets for prognosis and drug treatment of TAD in the future.

Local upregulation of interleukin-1 beta in aortic dissecting aneurysm: correlation with matrix metalloproteinase-2, 9 expression and biomechanical decrease.

OBJECTIVES: Our goal was to examine whether interleukin-1 beta (IL-1ß) originates locally and its possible relationship with matrix metalloproteinases (MMPs), apoptosis, elastin fibres and biomechanics in aortic dissecting aneurysms (DAs). METHODS: Aortic DAs were induced in 24 rats with ß-aminopropionitrile (BAPN); another 12 rats without BAPN were designated as controls. Then IL-1ß levels were measured both in the circulation and in local aortic specimens. The expression of MMP-2 and MMP-9 and Victoria blue and TUNEL staining were also detected. Biomechanical parameters such as the elasticity modulus were used to detect the biomechanical changes in the aortic wall. The correlation of IL-1ß, MMP-2, MMP-9, apoptosis and biomechanical properties was analysed. RESULTS: Seventeen rats (17/24, 71%) in the BAPN-treated group died of DA rupture. IL-1ß levels were dramatically increased in the DA specimens but not in the circulation. Victoria blue staining confirmed the formation of the DA and the reduction of elastin content after induction by BAPN. The extent of apoptosis in the aortic media was dramatically higher in rats with BAPN-induced DA than that in the control group and that in rats treated with BAPN but without DA. MMP-2 and MMP-9 levels were significantly increased in BAPN-treated rats compared to the controls, but no statistical significance was found between rats with and without DA. There were significant differences in biomechanical parameters, such as the elasticity modulus. Among the 3 groups, IL-1ß was positively correlated with MMP-2 and MMP-9 levels and with the elasticity modulus but not with apoptosis. CONCLUSIONS: Local IL-1ß might participate in the formation of aortic DA through the upregulation of MMP-2 and MMP-9 and the breakage of elastin fibres, which finally weakens the biomechanical properties of the aortic wall.