Selenoprotein deficiency disorder predisposes to aortic aneurysm formation.
Selenoprotein deficiency disorder predisposes to aortic aneurysm formation.
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硒蛋白缺乏症容易形成主动脉瘤。
DOI：
10.1038/s41467-023-43851-6
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发表时间：
2023-12-02
影响因子：
16.6
通讯作者：
Chatterjee K
中科院分区：
文献类型：
--
作者：
Schoenmakers E;Marelli F;Jørgensen HF;Visser WE;Moran C;Groeneweg S;Avalos C;Jurgens SJ;Figg N;Finigan A;Wali N;Agostini M;Wardle-Jones H;Lyons G;Rusk R;Gopalan D;Twiss P;Visser JJ;Goddard M;Nashef SAM;Heijmen R;Clift P;Sinha S;Pirruccello JP;Ellinor PT;Busch-Nentwich EM;Ramirez-Solis R;Murphy MP;Persani L;Bennett M;Chatterjee K
主动脉瘤可能会急性分离或破裂并致命，可能是具有遗传基础的多系统疾病的一部分。我们报告了4例由于硒代半胱氨酸插入序列结合蛋白2（SECISBP2）突变导致的含硒半胱氨酸蛋白缺乏的患者，这些患者由于囊性中膜坏死而表现出早发性、进行性、动脉瘤样扩张的升主动脉。具有Secisbp2的全局或血管平滑肌细胞（VSMC）靶向破坏的斑马鱼和雄性小鼠分别显示类似的异位症。患者和动物模型的主动脉表现出细胞活性氧升高，DNA氧化损伤和VSMC凋亡。铁的抗氧化剂暴露或螯合防止患者细胞中的氧化损伤和斑马鱼模型中的脊椎病。我们的观察结果表明，氧化应激和细胞死亡，包括通过铁凋亡，在介导主动脉变性的关键作用。主动脉瘤有遗传基础。在这里，作者报告说，硒蛋白缺乏症由于SECISBP 2突变，导致氧化应激介导的主动脉细胞死亡，诱发胸主动脉瘤形成。
Aortic aneurysms, which may dissect or rupture acutely and be lethal, can be a part of multisystem disorders that have a heritable basis. We report four patients with deficiency of selenocysteine-containing proteins due to selenocysteine Insertion Sequence Binding Protein 2 (SECISBP2) mutations who show early-onset, progressive, aneurysmal dilatation of the ascending aorta due to cystic medial necrosis. Zebrafish and male mice with global or vascular smooth muscle cell (VSMC)-targeted disruption of Secisbp2 respectively show similar aortopathy. Aortas from patients and animal models exhibit raised cellular reactive oxygen species, oxidative DNA damage and VSMC apoptosis. Antioxidant exposure or chelation of iron prevents oxidative damage in patient’s cells and aortopathy in the zebrafish model. Our observations suggest a key role for oxidative stress and cell death, including via ferroptosis, in mediating aortic degeneration. Aortic aneurysms have a heritable basis. Here, the authors report that a selenoprotein deficiency disorder due to mutations in SECISBP2, causes oxidative stress-mediated aortic cell death, predisposing to thoracic aortic aneurysm formation.
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影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
影响因子：
12.3
作者：
McLaren W;Gil L;Hunt SE;Riat HS;Ritchie GR;Thormann A;Flicek P;Cunningham F
通讯作者：
Cunningham F
影响因子：
5.6
作者：
Cao RY;Amand T;Ford MD;Piomelli U;Funk CD
通讯作者：
Funk CD
影响因子：
64.8
作者：
Karczewski, Konrad J;Francioli, Laurent C;MacArthur, Daniel G
通讯作者：
MacArthur, Daniel G