Review of Current Theories for Abdominal Aortic Aneurysm Pathogenesis
Review of Current Theories for Abdominal Aortic Aneurysm Pathogenesis
Atherosclerotic plaques are a feature of abdominal aortic aneurysms (AAAs). Atherosclerosis and AAA appear to share similar risk factors. These observations have led to the conclusion that AAAs are a consequence of advanced atherosclerosis.
This review explores current theories regarding the pathogenesis of AAA and their implications for treatment.
A systematic literature search was conducted using the search terms abdominal aortic aneurysm, atherosclerosis, pathogenesis, and systemic disease. Articles were categorized according to the association of AAAs with atherosclerosis, arteriomegaly, peripheral aneurysm, systemic expression, genetics, autoimmunity, oxidative stress, and systemic disease. Twenty-nine articles reporting changes in the systemic vasculature associated with AAA and 12 articles examining the shared risk factor hypothesis were identified.
There is insufficient evidence to confirm that AAAs are the result of advanced atherosclerosis. The bulk of evidence points to AAA disease being a systemic disease of the vasculature, with a predetermined genetic susceptibility leading to a phenotype governed by environmental factors.
Abdominal aortic aneurysm (AAA) is a permanent localized dilatation of the abdominal aorta encompassing all three layers of the vessel wall that exceeds the normal diameter by 50%. The underlying problem is a weakening in the aortic wall that leads to progressive dilatation, which, if left untreated, may result in rupture and death. It is estimated to be the tenth most common cause of mortality and accounts for 2% of all deaths; up to 8% of men over 60 years are now affected. The pathogenesis of AAA remains poorly understood; however, recent evidence has confirmed the significance of a chronic inflammatory process, particularly related to an upregulation of matrix metalloproteinases (MMPs).
Several significant risk factors for the development of AAAs have been identified. These include male sex, age, family history, and smoking. Whereas hypertension has been shown to increase growth rate in already established AAAs, diabetes has been shown to be protective. The incidence of AAA is increasing despite a reduction in tobacco use and an ever-increasing incidence of diabetes. This has led to uncertainty as to the significance of these risk factors in aneurysm pathogenesis.
The arterial wall is an organ capable of remodeling in response to hemodynamic, mechanical, and biochemical stimuli. Throughout its lifetime, the living components of the arterial wall must regenerate and remodel continuously to maintain the integrity and function of the system and to withstand the repetitive wall stresses.
AAA formation appears to be a focal event, yet patients with AAAs often have aneurysms at sites remote from the abdominal aorta. This initially raised the suspicion that aortic aneurysms are a local representation of a systemic dilating diathesis.
There are three possible models of AAA pathogenesis. First, AAAs could be a purely local disease process confined to the abdominal aorta resulting from atherosclerosis. Second, aneurysms in the aorta may be representative of a systemic dilating diathesis primarily governed by genotype. Third, the changes in the abdominal aorta may be a demonstration of a globally sick or diseased vascular tree as a consequence of a chronic inflammatory process. The three proposed hypotheses are not mutually exclusive. The genotype may influence the inflammatory response, and, equally, the inflammatory cells and mechanical forces may modify gene expression. The evidence for a systemic process with focal manifestation in the abdominal aorta is diverse but as yet not categorical.
In this review, we examine the question of whether AAAs are a consequence of atherosclerosis and explore the argument that AAAs are actually a local representation of a systemic disease of the vasculature.
Abstract and Introduction
Abstract
Atherosclerotic plaques are a feature of abdominal aortic aneurysms (AAAs). Atherosclerosis and AAA appear to share similar risk factors. These observations have led to the conclusion that AAAs are a consequence of advanced atherosclerosis.
This review explores current theories regarding the pathogenesis of AAA and their implications for treatment.
A systematic literature search was conducted using the search terms abdominal aortic aneurysm, atherosclerosis, pathogenesis, and systemic disease. Articles were categorized according to the association of AAAs with atherosclerosis, arteriomegaly, peripheral aneurysm, systemic expression, genetics, autoimmunity, oxidative stress, and systemic disease. Twenty-nine articles reporting changes in the systemic vasculature associated with AAA and 12 articles examining the shared risk factor hypothesis were identified.
There is insufficient evidence to confirm that AAAs are the result of advanced atherosclerosis. The bulk of evidence points to AAA disease being a systemic disease of the vasculature, with a predetermined genetic susceptibility leading to a phenotype governed by environmental factors.
Introduction
Abdominal aortic aneurysm (AAA) is a permanent localized dilatation of the abdominal aorta encompassing all three layers of the vessel wall that exceeds the normal diameter by 50%. The underlying problem is a weakening in the aortic wall that leads to progressive dilatation, which, if left untreated, may result in rupture and death. It is estimated to be the tenth most common cause of mortality and accounts for 2% of all deaths; up to 8% of men over 60 years are now affected. The pathogenesis of AAA remains poorly understood; however, recent evidence has confirmed the significance of a chronic inflammatory process, particularly related to an upregulation of matrix metalloproteinases (MMPs).
Several significant risk factors for the development of AAAs have been identified. These include male sex, age, family history, and smoking. Whereas hypertension has been shown to increase growth rate in already established AAAs, diabetes has been shown to be protective. The incidence of AAA is increasing despite a reduction in tobacco use and an ever-increasing incidence of diabetes. This has led to uncertainty as to the significance of these risk factors in aneurysm pathogenesis.
The arterial wall is an organ capable of remodeling in response to hemodynamic, mechanical, and biochemical stimuli. Throughout its lifetime, the living components of the arterial wall must regenerate and remodel continuously to maintain the integrity and function of the system and to withstand the repetitive wall stresses.
AAA formation appears to be a focal event, yet patients with AAAs often have aneurysms at sites remote from the abdominal aorta. This initially raised the suspicion that aortic aneurysms are a local representation of a systemic dilating diathesis.
There are three possible models of AAA pathogenesis. First, AAAs could be a purely local disease process confined to the abdominal aorta resulting from atherosclerosis. Second, aneurysms in the aorta may be representative of a systemic dilating diathesis primarily governed by genotype. Third, the changes in the abdominal aorta may be a demonstration of a globally sick or diseased vascular tree as a consequence of a chronic inflammatory process. The three proposed hypotheses are not mutually exclusive. The genotype may influence the inflammatory response, and, equally, the inflammatory cells and mechanical forces may modify gene expression. The evidence for a systemic process with focal manifestation in the abdominal aorta is diverse but as yet not categorical.
In this review, we examine the question of whether AAAs are a consequence of atherosclerosis and explore the argument that AAAs are actually a local representation of a systemic disease of the vasculature.
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