Ascending Aortic Proaneurysmal Genetic Mutations with Antiatherogenic Effects

Thoracic aortic aneurysms are common and are associated with a high morbidity and mortality. Despite this lethal diagnosis, there is an increasing body of evidence to suggest that the diagnosis of an aneurysm, specifically in the ascending thoracic aorta, may significantly reduce the risk of developing systemic atherosclerosis. Clinical observations in the operating room have shown pristine blood vessels in patients undergoing surgery for thoracic aortic aneurysms. There is now evidence that both the carotid intima-media thickness and arterial calcification, which are early and late signs of atherosclerosis respectively, are decreased in those with thoracic aortic aneurysms. These clinical studies are supported by molecular, genetic, and pharmacological evidence. Two principle mechanisms have been identified to explain the relationship of a proaneurysmal state conferring protection from atherosclerosis. These include an excess proteolytic balance of matrix metalloproteinase activity, leading to fragmentation of elastic lamellae and disordered collagen deposition. In addition, transforming growth factor β modulates vascular smooth muscle cells, extracellular matrix, and leukocytes. This confers protection from the initial plaque formation and, later provides stability to the plaque possibly through alteration of the types I and II transforming growth factor β receptor ratio. Furthermore, studies are now beginning to establish an important role for statins and estradiol in modulating these complex pathways. In the future, as our understanding of these complex mechanisms underlying aneurysmal protection against atherosclerosis increases, corresponding therapies may be developed to offer protection from atherosclerosis.