Genetics of Thoracic Aortic Aneurysm: At the Crossroad of Transforming Growth Factor- Signaling and Vascular Smooth Muscle Cell Contractility

被引:135
作者
Gillis, Elisabeth [1 ,2 ]
Van Laer, Lut [1 ,2 ]
Loeys, Bart L. [1 ,2 ,3 ]
机构
[1] Univ Antwerp, Fac Med & Hlth Sci, Ctr Med Genet, B-2020 Antwerp, Belgium
[2] Univ Antwerp Hosp, Antwerp, Belgium
[3] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands
基金
欧洲研究理事会;
关键词
aortic aneurysm; thoracic; Loeys-Dietz syndrome; Marfan syndrome; TGF-; signaling; vascular smooth muscle cell; EHLERS-DANLOS-SYNDROME; BETA BINDING-PROTEIN; SHPRINTZEN-GOLDBERG-SYNDROME; GENOME-WIDE ASSOCIATION; TGF-BETA; MARFAN-SYNDROME; SEQUENCE VARIANT; CUTIS LAXA; MATRIX METALLOPROTEINASES; OSTEOGENESIS IMPERFECTA;
D O I
10.1161/CIRCRESAHA.113.300675
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Aortic aneurysm, including both abdominal aortic aneurysm and thoracic aortic aneurysm, is the cause of death of 1% to 2% of the Western population. This review focuses only on thoracic aortic aneurysms and dissections. During the past decade, the genetic contribution to the pathogenesis of thoracic aortic aneurysms and dissections has revealed perturbed extracellular matrix signaling cascade interactions and deficient intracellular components of the smooth muscle contractile apparatus as the key mechanisms. Based on the study of different Marfan mouse models and the discovery of several novel thoracic aortic aneurysm genes, the involvement of the transforming growth factor- signaling pathway has opened unexpected new avenues. Overall, these discoveries have 3 important consequences. First, the pathogenesis of thoracic aortic aneurysms and dissections is better understood, although some controversy still exists. Second, the management strategies for the medical and surgical treatment of thoracic aortic aneurysms and dissections are becoming increasingly gene-tailored. Third, the pathogenetic insights have delivered new treatment options that are currently being investigated in large clinical trials.
引用
收藏
页码:327 / 340
页数:14
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