Interleukin-1beta Medical Therapy Reduces the Risk of Thoracic Aortic Dissection in Rodent Model

Abstract

Introduction: Thoracic Aortic Dissection (TAD) are associated with matrix changes and biochemical changes in the aortic wall. Several studies proved a relationship between inflammatory markers, in example IL-1s, and these matrix changes. However, the exact mechanism is yet still unknown. Therefore, we investigated the role of IL-1s, MMP-2, MMP-9, smooth muscle cell (SMC) apoptosis and elastic fiber fracture in the development of TAD in rat. Methods: TAD was investigated in 96 male Sprague-Dawley rats which were divided in 4 groups equally (Control, BAPN, BAPN IL-1s and BAPN IL-1s antibody). Rats were monitored for 6 weeks in which systolic blood pressure, survival and the development of TAD were measured. After termination aortic tissue was harvested. Expression of IL-1s, MMP-2 and MMP-9 was measured by western blot. Apoptosis was measured by TUNEL assay and aorta elastin concentration by Victoria blue staining. Additionally, biomechanical characteristics were measured in-vitro. Results: Blood pressures were equal between groups. Mortality differed significantly between groups (control 0%, BAPN; 54.2%, BAPN IL-1s 75% and BAPN anti-IL-1s 37.5%), as was the occurrence of TAD (control 0%, BAPN 45.8, BAPN IL- 75%, anti-IL-1s 37.5%). Aneurysm diameters varied between groups (control 1.13±0.05mm, BAPN 3.48±0.42mm, BAPN IL-1s 5.33±0.42mm, BAPN anti-IL-1s 2.4±0.35mm). Relative elastin area to the total vascular wall significantly differed between groups (control 6.53±0.58%, BAPN 3.47±0.50%, BAPN IL1s 2.98±0.57%, BAPN anti-IL-1s 3.87±.058%) Conclusion: In this study IL-1s may have led to increased formation of TAD. On the contrary anti-IL-1s therapy significantly reduced death in rats, which may be explained by a reduction in the expression of MMP-2, MMP-9 and degradation the aortic wall matrix. These results can be seen as the basis for selective drug treatment of TAD. Funding Statement: This work was supported by National Natural Science Foundation of 15 China (81200225) and Talent Development Fund of Shanghai(2017038) Declaration of Interests: None declared. Ethics Approval Statement: All the procedures on the rats were approved by the Ethics Committee for Animal Experimentation and conducted according to the Guidelines for Animal Experimentation of our institutes.