Genetic basis of thoracic aortic aneurysms and dissections

Abstract

The major diseases affecting the aorta are aortic aneurysms and dissections, which are classified based on anatomic location. Diseases affecting the ascending aorta, such as thoracic aortic aneurysms and type I and II dissections, are primarily associated with medial necrosis on pathologic examination. Medial necrosis is characterized by fragmentation and loss of elastic fibers, loss of smooth muscle cells, and interstitial collections of collagenous tissue and basophilic ground substance. Medial necrosis occurs as part of the normal aging of the aorta but is accelerated by other conditions, including hypertension and genetic alterations that predispose persons to these aortic diseases. The etiologies of many of the genetic syndromes, such as Marfan syndrome, that predispose persons to thoracic aortic aneurysms and dissections are understood. Studies are just beginning to elucidate the genes that predispose persons without known syndromes to these aortic diseases, and a major locus for this condition, termed the TAAD1 locus, has been mapped to 5q13-14. Future characterization of this gene and others will enhance the ability to determine persons at risk for aortic aneurysms and dissections and will define molecular mechanisms involved in the pathogenesis of this disorder.