Diabetes:糖尿病依赖细胞分裂自身抗体(CDA1)发挥抗动脉瘤形成的作用。

2018-01-10 qinqiyun MedSci原创

糖尿病是动脉瘤的负性危险因子,但对于该现象的潜在机制尚不明确。Jiaze Li等人既往发现可强化TGF-β信号的细胞分裂自身抗体1(CDA1)在糖尿病患者中表达上调,因此推测,CDA1在糖尿病抗动脉瘤的保护作用中发挥关键作用。研究人员为验证上述推测,建立雄性野生型、CDA1敲除型、载脂蛋白E(ApoE)敲除型和CDA1/ApoE双敲除型(dKO)的糖尿病小鼠模型。结果,在ApoE敲除型和野生型小鼠

糖尿病是动脉瘤的负性危险因子,但对于该现象的潜在机制尚不明确。Jiaze Li等人既往发现可强化TGF-β信号的细胞分裂自身抗体1(CDA1)在糖尿病患者中表达上调,因此推测,CDA1在糖尿病抗动脉瘤的保护作用中发挥关键作用。

研究人员为验证上述推测,建立雄性野生型、CDA1敲除型、载脂蛋白E(ApoE)敲除型和CDA1/ApoE双敲除型(dKO)的糖尿病小鼠模型。

结果,在ApoE敲除型和野生型小鼠中,均为发现动脉瘤,40%的dKO小鼠出现动脉瘤。这些动脉瘤的发生与动脉TGF-β信号减弱、多种胶原蛋白表达下调以及动脉巨噬细胞浸润增加、基质金属蛋白酶12表达上调相关。

利用血管紧张素II(AngII)诱导动脉瘤形成的经典发现,合并糖尿病可减少致命性动脉破裂的风险、并可减弱肾上腺性的动脉扩展,而这些改变在dKO小鼠中未见。此外,人类腹主动脉瘤的活检动脉中CDA1表达下调高达70%。

综上所述,糖尿病与血管CDA1表达上调相关;而糖尿病小鼠CDA1缺失促进动脉瘤的形成,则支持CDA1在糖尿病减少动脉瘤形成的易感性中发挥一定作用这一推论。

原始出处:

Jiaze Li,et al.Diabetes Reduces Severity of Aortic Aneurysms Depending on the Presence of Cell Division Autoantigen 1 (CDA1).Diabetes  2018 Jan;  db170134.  https://doi.org/10.2337/db17-0134

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