Genetic basis of thoracic aortic aneurysms and dissections: focus on smooth muscle cell contractile dysfunction.
Thoracic aortic aneurysms leading to type A dissections (TAAD) can be inherited in isolation or in association with genetic syndromes, such as Marfan syndrome and Loeys-Dietz syndrome. When TAAD occurs in the absence of syndromic features, it is inherited in an autosomal dominant manner with decreased penetrance and variable expression, the disease is referred to as familial TAAD. Familial TAAD exhibits significant clinical and genetic heterogeneity. The first genes identified to cause TAAD were FBN1, TGFBR2, and TGFBR1. The identification and characterization of these genes suggested that increased TGF-beta signaling plays a role in pathogenesis. The recent discovery that mutations in the vascular smooth muscle cell (SMC)-specific beta-myosin (MYH11) and alpha-actin (ACTA2) can also cause this disorder has focused attention on the importance of the maintenance of SMC contractile function in preserving aortic structure and preventing TAAD.
Milewicz
Dianna M
DM
Department of Internal Medicine, University of Texas, Houston, Texas 77030, USA. Dianna.M.Milewicz@uth.tmc.edu
Guo
Dong-Chuan
DC
Tran-Fadulu
Van
V
Lafont
Andrea L
AL
Papke
Christina L
CL
Inamoto
Sakiko
S
Kwartler
Carrie S
CS
Pannu
Hariyadarshi
H
D000784:Aortic Dissection / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D000818:Animals; D017545:Aortic Aneurysm, Thoracic / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D005260:Female; D006801:Humans; D008297:Male; D008957:Models, Genetic; D009119:Muscle Contraction / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology; D009154:Mutation; D010375:Pedigree; D013577:Syndrome