Genetic and Epigenetic Mechanisms Underlying Vascular Smooth Muscle Cell Phenotypic Modulation in Abdominal Aortic Aneurysm.
Genetic and Epigenetic Mechanisms Underlying Vascular Smooth Muscle Cell Phenotypic Modulation in Abdominal Aortic Aneurysm.
复制标题
腹主动脉瘤血管平滑肌细胞表型调节的遗传和表观遗传机制。
DOI：
10.3390/ijms21176334
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发表时间：
2020-08-31
影响因子：
5.6
通讯作者：
Sorokin V
中科院分区：
文献类型：
--
作者：
Gurung R;Choong AM;Woo CC;Foo R;Sorokin V
腹主动脉瘤（AAA）是指肾下主动脉的局限性扩张，其中直径超过3.0 cm。血管平滑肌细胞损失、细胞外基质（ECM）降解、血管炎症和氧化应激是AAA发病机制的标志，并导致主动脉壁的中膜和外膜进行性变薄。随着腹主动脉瘤直径的增加，如果不及时治疗，主动脉破裂的发生率很高。最近的遗传学和表观遗传学研究的集体证据表明，平滑肌细胞（SMC）向去分化和增殖状态的表型调节，这与血管壁的ECM重塑相关，并伴随着细胞衰老和炎症的增加，在体外和体内疾病模型中可见。这篇评论批判性地分析了现有的出版物中涉及的复杂作用的主动脉壁内的SMC在AAA形成的遗传和表观遗传机制，并反映了SMC的可塑性在AAA形成的重要性。尽管来自各种小鼠模型的证据令人信服，但如何将这些知识应用于人类生物学，迫切需要利用现代体外和体内实验技术来解决。
Abdominal aortic aneurysm (AAA) refers to the localized dilatation of the infra-renal aorta, in which the diameter exceeds 3.0 cm. Loss of vascular smooth muscle cells, degradation of the extracellular matrix (ECM), vascular inflammation, and oxidative stress are hallmarks of AAA pathogenesis and contribute to the progressive thinning of the media and adventitia of the aortic wall. With increasing AAA diameter, and left untreated, aortic rupture ensues with high mortality. Collective evidence of recent genetic and epigenetic studies has shown that phenotypic modulation of smooth muscle cells (SMCs) towards dedifferentiation and proliferative state, which associate with the ECM remodeling of the vascular wall and accompanied with increased cell senescence and inflammation, is seen in in vitro and in vivo models of the disease. This review critically analyses existing publications on the genetic and epigenetic mechanisms implicated in the complex role of SMCs within the aortic wall in AAA formation and reflects the importance of SMCs plasticity in AAA formation. Although evidence from the wide variety of mouse models is convincing, how this knowledge is applied to human biology needs to be addressed urgently leveraging modern in vitro and in vivo experimental technology.
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影响因子：
1.5
作者：
Akerman AW;Stroud RE;Barrs RW;Grespin RT;McDonald LT;LaRue RAC;Mukherjee R;Ikonomidis JS;Jones JA;Ruddy JM
通讯作者：
Ruddy JM
影响因子：
5.3
作者：
CAMPA, JS;GREENHALGH, RM;POWELL, JT
通讯作者：
POWELL, JT
影响因子：
9.8
作者：
Bown, Matthew J.;Jones, Gregory T.;Samani, Nilesh J.
通讯作者：
Samani, Nilesh J.
影响因子：
5.3
作者：
Biros, Erik;Norman, Paul E.;Golledge, Jonathan
通讯作者：
Golledge, Jonathan
影响因子：
4.1
作者：
Bernardo, MM;Fridman, R
通讯作者：
Fridman, R