Molecular Mechanisms in Genetic Aortopathy-Signaling Pathways and Potential Interventions.
Molecular Mechanisms in Genetic Aortopathy-Signaling Pathways and Potential Interventions.
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DOI：
10.3390/ijms24021795
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发表时间：
2023-01-16
影响因子：
5.6
通讯作者：
Jeremy, Richmond
中科院分区：
文献类型：
--
作者：
Dong, Charlotte Xue;Malecki, Cassandra;Robertson, Elizabeth;Hambly, Brett;Jeremy, Richmond
胸主动脉疾病影响所有年龄段的人，大多数年龄<60岁的人都有潜在的遗传原因。目前胸主动脉瘤尚无有效的药物治疗方法，手术仍是主要的干预手段。腹主动脉瘤的炎症/动脉粥样硬化发病机制已得到很好的证实，而胸主动脉瘤的发病机制尚不清楚。本文研究了负责主动脉生长和发育的关键细胞信号系统，内皮细胞和血管平滑肌细胞的稳态以及通路之间的相互作用。证据支持的作用，个别信号通路在胸主动脉瘤的发病机制进行审查和潜在的新的治疗方法进行审查。几种关键的信号传导途径，特别是TGF-β、WNT、NOTCH、PI 3 K/AKT和ANGII有助于血管平滑肌和内皮细胞的生长、增殖、细胞表型和存活。通路之间以及血管平滑肌和内皮细胞之间存在串扰，具有协同和拮抗相互作用。每一种激活的共同特征是对损伤或异常细胞应激的反应。相当多的实验证据支持这些途径中的每一个对动脉瘤形成的贡献。虽然人类的资料较少，但有足够的数据来暗示人类胸主动脉瘤的发病机制中的每一个途径。作为一些途径，即，WNT和NOTCH在生命早期的组织生长和器官发生中起关键作用，这些途径的失调可能导致异常的主动脉结构，即使在婴儿期，从而为以后的动脉瘤发展奠定基础。鉴于这些信号系统的微调，关键信号元件的功能多态性可能会导致未来发生胸动脉瘤的风险。已经开发了多种新型治疗剂，靶向细胞信号传导途径，主要用于癌症药物。未来的研究解决细胞特异性靶向，降低毒性，也不太激烈的治疗效果可能持有的承诺，有效的新的医学治疗胸主动脉瘤。
Thoracic aortic disease affects people of all ages and the majority of those aged <60 years have an underlying genetic cause. There is presently no effective medical therapy for thoracic aneurysm and surgery remains the principal intervention. Unlike abdominal aortic aneurysm, for which the inflammatory/atherosclerotic pathogenesis is well established, the mechanism of thoracic aneurysm is less understood. This paper examines the key cell signaling systems responsible for the growth and development of the aorta, homeostasis of endothelial and vascular smooth muscle cells and interactions between pathways. The evidence supporting a role for individual signaling pathways in pathogenesis of thoracic aortic aneurysm is examined and potential novel therapeutic approaches are reviewed. Several key signaling pathways, notably TGF-β, WNT, NOTCH, PI3K/AKT and ANGII contribute to growth, proliferation, cell phenotype and survival for both vascular smooth muscle and endothelial cells. There is crosstalk between pathways, and between vascular smooth muscle and endothelial cells, with both synergistic and antagonistic interactions. A common feature of the activation of each is response to injury or abnormal cell stress. Considerable experimental evidence supports a contribution of each of these pathways to aneurysm formation. Although human information is less, there is sufficient data to implicate each pathway in the pathogenesis of human thoracic aneurysm. As some pathways i.e., WNT and NOTCH, play key roles in tissue growth and organogenesis in early life, it is possible that dysregulation of these pathways results in an abnormal aortic architecture even in infancy, thereby setting the stage for aneurysm development in later life. Given the fine tuning of these signaling systems, functional polymorphisms in key signaling elements may set up a future risk of thoracic aneurysm. Multiple novel therapeutic agents have been developed, targeting cell signaling pathways, predominantly in cancer medicine. Future investigations addressing cell specific targeting, reduced toxicity and also less intense treatment effects may hold promise for effective new medical treatments of thoracic aortic aneurysm.
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影响因子：
4.8
作者：
Allard, David;Figg, Nichola;Littlewood, Trevor D.
通讯作者：
Littlewood, Trevor D.
影响因子：
4.8
作者：
Abid, MR;Yano, K;Aird, WC
通讯作者：
Aird, WC
Notch 和 TGF-β 信号通路之间的串扰由 Notch 胞内结构域与 Smad3 的相互作用介导。
影响因子：
7.8
作者：
Blokzijl, A;Dahlqvist, C;Reissmann, E;Falk, A;Moliner, A;Lendahl, U;Ibáñez, CF
通讯作者：
Ibáñez, CF
DOI：
10.4081/ejh.2014.2383
发表时间：
2014-07-18
期刊：
European journal of histochemistry : EJH
影响因子：
--
作者：
Arcucci A;Ruocco MR;Albano F;Granato G;Romano V;Corso G;Bancone C;De Vendittis E;Della Corte A;Montagnani S
通讯作者：
Montagnani S
影响因子：
8.3
作者：
BENETOS, A;TOPOUCHIAN, J;CAMBIEN, F
通讯作者：
CAMBIEN, F