Analysis of extracellular superoxide dismutase and Akt in ascending aortic aneurysm with tricuspid or bicuspid aortic valve.
Analysis of extracellular superoxide dismutase and Akt in ascending aortic aneurysm with tricuspid or bicuspid aortic valve.
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DOI：
10.4081/ejh.2014.2383
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发表时间：
2014-07-18
期刊：
影响因子：
--
通讯作者：
Montagnani S
中科院分区：
文献类型：
--
作者：
Arcucci A;Ruocco MR;Albano F;Granato G;Romano V;Corso G;Bancone C;De Vendittis E;Della Corte A;Montagnani S
升主动脉瘤（AsAA）是内侧退行性变（MD）的结果，源于平滑肌细胞（SMC）的凋亡损失以及弹性蛋白和胶原纤维的断裂。细胞外基质结构和蛋白质组成的改变，典型的内侧变性，可以调节细胞内通路。在本研究中，我们研究了细胞外超氧化物歧化酶（SOD3）和Akt在AsAA发病机制中的相关性，评估了它们在对照组（n=6）、AsAA合并三尖瓣主动脉瓣（TAV, n=9）或二尖瓣主动脉瓣（BAV, n=9）患者升主动脉组织中的组织分布和蛋白水平。结果显示，与对照组相比，BAV患者AsAA组织中SOD3、磷酸化Akt和Akt蛋白水平显著降低，而对照组和TAV患者之间的差异不显著。BAV主动脉组织中SOD3和Akt水平降低与Erk1/Erk2磷酸化降低和MMP-9水平升高有关。作者认为，SOD3蛋白水平降低在BAV相关的AsAA进展中起作用，并且在BAV相关的主动脉病变晚期，主动脉介质层的ECM修饰与Erk1/Erk2和Akt信号受损之间存在联系。
Ascending aortic aneurysm (AsAA) is a consequence of medial degeneration (MD), deriving from apoptotic loss of smooth muscle cells (SMC) and fragmentation of elastin and collagen fibers. Alterations of extracellular matrix structure and protein composition, typical of medial degeneration, can modulate intracellular pathways. In this study we examined the relevance of extracellular superoxide dismutase (SOD3) and Akt in AsAA pathogenesis, evaluating their tissue distribution and protein levels in ascending aortic tissues from controls (n=6), patients affected by AsAA associated to tricuspid aortic valve (TAV, n=9) or bicuspid aortic valve (BAV, n=9). The results showed a significant reduction of SOD3, phospho-Akt and Akt protein levels in AsAA tissues from patients with BAV, compared to controls, whereas the differences observed between controls and patients with TAV were not significant. The decreased levels of SOD3 and Akt in BAV aortic tissues are associated with decreased Erk1/Erk2 phosphorylation and MMP-9 levels increase. The authors suggest a role of decreased SOD3 protein levels in the progression of AsAA with BAV and a link between ECM modifications of aortic media layer and impaired Erk1/Erk2 and Akt signaling in the late stages of the aortopathy associated with BAV.
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DOI：
10.1126/science.1192149
发表时间：
2011-04-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Holm TM;Habashi JP;Doyle JJ;Bedja D;Chen Y;van Erp C;Lindsay ME;Kim D;Schoenhoff F;Cohn RD;Loeys BL;Thomas CJ;Patnaik S;Marugan JJ;Judge DP;Dietz HC
通讯作者：
Dietz HC
影响因子：
3.7
作者：
Laatikainen LE;Incoronato M;Castellone MD;Laurila JP;Santoro M;Laukkanen MO
通讯作者：
Laukkanen MO
影响因子：
4.8
作者：
Ushio-Fukai, M;Alexander, RW;Griendling, KK
通讯作者：
Griendling, KK
影响因子：
20.1
作者：
Shen YH;Zhang L;Ren P;Nguyen MT;Zou S;Wu D;Wang XL;Coselli JS;LeMaire SA
通讯作者：
LeMaire SA
影响因子：
20.1
作者：
Xiong W;Meisinger T;Knispel R;Worth JM;Baxter BT
通讯作者：
Baxter BT