| Objective:Inflammatory reaction has been thought to be one of the mechanisms in generation and progression of ascending thoracic aortic aneurysms(TAA) and type I thoracic aortic dissections(TAD).This study sought to 1)determine whether the classic inflammatory mediators(interleukin-1βand interferon-γ) are present in medial degeneration and assess any possible contribution of the mediators to apoptosis of aortic artery wall cells and degradation of media matrix.2)detect the relationship between signal transduction protein(P-p38 and P-JNK) and expression of interleukin-1β(IL-1β) and interferon-γ(IFN-γ).Methods:1)Aortic specimens were obtained from patients undergoing prophylactic surgical repair of type I TAD(n = 11) and ascending TAA(n = 10),along with control patients dying of causes unrelated to aortic disease (n=7).TUNEL staining were used to detect the apoptosis of vessel cells such as smooth muscle cells and inflammatory cells in the aortas of patients with ascending TAA and type I TAD.Immunohistochemical staining were performed to evaluate the presence of IL-1β,IFN-γand matrix metalloproteinase-9(MMP-9).Western blot analysis and real-time PCR were used to measure the exact content of the protein and mRNA of IL-1βand IFN-γ.Then the correlation between TUNEL staining,IL-1β,IFN-γ,MMP-9 expression and some clinical parameters such as age, hypertension,smoking,leukocyte,and maximal diameter of aortic wall were analyzed.2) Immunohistochemical staining and western blot analysis were used to detect the expression and localization of P-p38 and P-JNK.Then the correlation of expression between P-p38 and the two mediators were analyzed.Results:1)Hematoxylin staining,western blot analysis and real-time PCR showed IL-1βexpressed highly in TAA and TAD than control group(P＜.0001),mainly located in the cytoplasm of smooth muscle cells(SMCs) and inflammatory cells such as T lymphocytes and macrophages. IFN-γexpressed highly in TAA than TAD and control group(P＜.0001 and P=0.0002),mainly located in inflammatory cells such as T lymphocytes and macrophages.There was no difference in the expression of IFN-γbetween TAD and control group(P=0.2335).2)There was positive correlation between the expression of IL-1βand MMP-9 in inflammatory cells of TAD.There was also positive correlation between expression of IFN-γand MMP-9 in inflammatory cells of TAA.3)There was more apoptosis in TAD and TAA than control group(P＜.0001 and P=0.0001).The expression of IFN-γin TAA had positive correlation with the diameter of aorta(P=0.0012).The expression of IFN-γin TAD had positive correlation with leucocyte and apoptosis (P=0.0025 and P=0.0212).The patients with hypertention had higher expression of IFN-γin inflammatory cells(P=0.0333).4) The content of p38 protein with phosphorylation had positive correlation with expression of IL-1βin TAD and TAA(P=0.0362和P=0.0416).The location of p38 and JNK protein with phosphorylation was similar with the location of IL-1βand IFN-γ.Conclusions:1) IL-1βand INF-γexpressed highly in TAA.INF-γmay increase the expression of MMP-9 in inflammatory cells in TAA which lead to the extension of aorta through the degradation of media matrix.Hypertention may also induce this process.2) IL-1βexpressed highly in TAD and it may improve the degradation of media matrix by increasing the expression of MMP-9 in inflammatory cells.IFN-γmay cause the apoptosis of vessel cells and induce the systematic inflammatory reaction in TAD.3) IL-1βand INF-γmay contribute to the generation or progression through signal transduction protein p38 and JNK with phosphorylation,but the exact mechanism need further study.
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