Abstract
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.
Keywords
aneurysm - atherosclerosis - estradiol - matrix metalloproteinases - statins - transforming
growth factor β - carotid intima-media thickness
