Genetics of Hereditary Large Vessel Diseases

Abstract

Abstract Recently, the genetic study of hereditary large vessel diseases such as Marfan syndrome has been advanced, leading to not only identifying pathogenic genes but also providing information of the pathophysiology and possible new therapeutic targets. Genes identified for hereditary large vessel diseases include FBN1 , TGFBR1 , TGFBR2 , SMAD3 , TGFB2 , TGFB3 , SKI , EFEMP2 , BGN , COL3A1 , FLNA , ACTA2 , MYH11 , MYLK , SLC2A10 and NOTCH1 . Dysfunction of these genes is mainly connected with altered function of transforming growth factor‐β (TGF‐β) signalling pathways, as well as that of the extracellular matrix or smooth muscle contractile apparatus, resulting in progression of structural abnormality to aorta and large vessels including aortic aneurysms and dissections. Furthermore, it has been shown that the TGF‐β signalling pathway plays a key role in the pathogenesis of Marfan syndrome and Loeys–Dietz syndrome, which may be important for development of strategies for medical and surgical treatment of hereditary large vessel diseases. Key Concepts Genetic study of hereditary large vessel diseases has been advanced. Young patients with large vessel diseases should be aware of possible genetic disease. Alteration of transforming growth factor‐β (TGF‐β) signalling pathways as well as that of the extracellular matrix or smooth muscle contractile apparatus is closely connected with large vessel diseases. Genetic study of hereditary large vessel diseases may help to get better therapeutic approach in the near future. Medical treatment modulating TGF‐β signaling would be effective for hereditary large vessel diseases.