Recent Advances in Molecular Mechanisms of Abdominal Aortic Aneurysm Formation

Abstract

Abdominal Aortic Aneurysm (AAA) is an increasingly common clinical condition with fatal implications. It is associated with advanced age, male gender, cigarette smoking, atherosclerosis, hypertension, and genetic predisposition. Although significant evidence has emerged in the last decade, the molecular mechanisms of AAA formation remains poorly understood. Currently, the treatment for AAA remains primarily surgical with the lone innovation of endovascular therapy. With advance in the human genome, understanding precisely which molecules and genes mediate AAA development and blocking their activity at the molecular level could lead to important new discoveries and therapies. This review summarizes recent updates in molecular mechanisms of AAA formation including animal models, autoimmune components, infection, key molecules and cytokines, mechanical forces, genetics and pharmacotherapy. This review will be helpful to those who want to recognize the newest endeavors within the field and identify possible lines of investigation in AAA.

Association of the TGF-β receptor genes with abdominal aortic aneurysm

“…A common feature of AAA is fragmentation of the elastic laminae and smooth muscle cell loss. 4 This may be the result of defective vascular remodeling, which under physiological circumstances induces adaptive changes within the vessel wall upon hemodynamic stress or as a response to vascular injury. Vascular remodeling includes a tightly regulated balance between degradation and rebuilding of the ECM.…”

“…Ultimately, vascular extracellular matrix (ECM) changes, accompanied by transmural inflammation, destructive remodeling of the elastic media, and depletion of medial smooth muscle cells, are observed. 4 This weakening of the vessel wall increases the risk of rupture with often a fatal outcome. Rupture rates increase with the size of the AAA, and therefore surgical intervention is considered when the AAA exceeds the 55 mm diameter threshold.…”

Perforin-Independent Extracellular Granzyme B Activity Contributes to Abdominal Aortic Aneurysm

“…1 The most significant risk factors for AAA are male gender, cigarette smoking, age, family history, and atherosclerotic disease. 2,3 The incidence of AAA measuring 2.9 to 4.9 cm in diameter ranges from 1.3% in men 45 to 54 years of age to 12.5% in men 75 to 84 years of age. In women, prevalence ranges from 0% to 5.2% in the same age groups.…”

Associations between common 3435 C>T variants of the multi-drug resistance [MDR-1 (ABCB1)] gene and abdominal aortic aneurysm: a pilot study

“…[13,14] Factors such as age, male gender, smoking, CAD, COPD, HT, DM cause adaptive alterations in AAA. [2,3,15] In our study, there were 33 individuals with HT, eight with HL, seven with DM, 10 with COPD, 21 with CAD and 21 smokers, while the mean age of patients with AAA was 62.9±6.6 years.…”

“…The male gender, smoking, atherosclerosis, high blood pressure, genetic factors and alterations in constitutions of elastin and collagen are considered to be responsible for the etiology. [1][2][3] Although the disease is associated with aging, atherosclerosis and familial tendency, its pathophysiology has not been revealed accurately. [1] The abdominal aortic aneurysm enlarges over time and if it has not been controlled, the final result is rupture.…”