Ascending Aortic Proaneurysmal Genetic Mutations with Antiatherogenic Effects

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.

Diabetes is not a negative prognostic factor for 30-days mortality after surgery for acute type A aortic dissection

“…However, CVD are the leading cause of death in patients with DM and the risk of CVD in patients with DM is more than double that of patients without DM [ 9 ]. However, the relationship between diabetes and aortic dissection is still not completely clear [ 10 , 11 ].…”

Risk Factors for Mortality From Aortic Aneurysm and Dissection: Results From a 26‐Year Follow‐Up of a Community‐Based Population

“…These findings may indicate that atherosclerosis plays a greater role in the pathogenesis of abdominal aortic aneurysm than in that of thoracic aortic aneurysm, as shown in previous studies. 27 , 28 , 29 A study comparing patients with ascending aortic aneurysm with controls showed less arterial calcification evaluated by computed tomography in the patients than in the controls. 27 Another study comparing the prevalence of coronary heart diseases and myocardial infarction in patients with a history of thoracic aortic aneurysm with that in controls identified a lower prevalence of coronary heart disease and myocardial infarction in the patients than in the controls.…”

“… 28 As for a biologic mechanism of thoracic aortic aneurysm, an excess proteolytic balance of matrix metalloproteinase activity, with transforming growth factor‐β modulating the extracellular matrix, is likely to lead to fragmentation of the elastic lamellae and disordered collagen deposition, which protects against plaque formation. 29 …”