The Relationship between the Concentration of Cathepsin A, D, and E and the Concentration of Copper and Zinc, and the Size of the Aneurysmal Enlargement in the Wall of the Abdominal Aortic Aneurysm

Abstract

Background: Despite advances in diagnostics and treatment, aortic aneurysms are an important clinical problem, mainly due to the accompanying complications that may lead to direct loss of life, also the number of diagnosed and operated aneurysms is constantly increasing. The aim of this study is to determine the relationship between the concentration of lysosomal peptidases cathepsin A, D, and E in the wall of the abdominal aortic aneurysm and the concentration of copper and zinc, and the size of the aneurysm widening in the wall of the abdominal aortic aneurysm. Methods: The study included 27 patients with abdominal aortic aneurysm from the Department of Vascular Surgery and Transplantation of the University Clinical Hospital in Bialystok. The research material was the wall of the abdominal aortic aneurysm collected intraoperatively. The control material consisted of fragments of the abdominal aorta obtained from organ donors for transplantation. The concentration of cathepsin A, D, and E was determined using enzymelinked immunosorbent assays. Concentrations of copper and zinc were determined by flame atomic absorption spectrometry after prior mineralization of the samples. All patients were interviewed and asked about basic demographic data, comorbidities, and risk factors for cardiovascular disease to which they were exposed in the past. The statistical analysis was performed using Statistica 10 statistical package. ManneWhitney U-tests were used and also Spearman's r correlation assuming a significance level of P < 0.05. Results: The concentration of cathepsin A, D, and E was higher in the aortic wall altered by the aneurysm than in the wall of the control aorta (P < 0.05). The analysis of the data showed that there was a positive correlation between the concentration of cathepsin A and D and the width of the aneurysmal widening (r ¼ 0.699 and 0.750, respectively). There was no correlation between cathepsin E concentration and aneurysm width. Conclusions: The higher contents of cathepsin A, D, and E in the wall of the aortic aneurysm than in the normal aortic wall, as well as a positive correlation between the concentration of cathepsin A and D and the width of the aneurysmal widening, allow to assume the participation of these enzymes in the pathogenesis of the aneurysm.

Extracellular matrix, regional heterogeneity of the aorta, and aortic aneurysm

“…Aortic aneurysm involves dramatic changes in the structural components of the vasculature, due to SMC dysfunction, imbalance between proteinases and their inhibitors, and abnormal synthesis, accumulation, or degradation of ECM proteins 3 . Among different classes of proteases, metalloproteinases (MMPs, ADAMs, and ADAM-TSs) 83,88,98,99 , and cathepsins 100,101 are important factors for pathogenesis of aneurysm, because of their involvement in cleavage of different ECM and non-ECM proteins. The availability of genetically modified mouse models has paved the way to understanding the role of the ECM and its remodeling, the importance of protease and their inhibitors, and the contribution of different proteoglycans and glycoproteins in aortic aneurysm.…”

“…Cathepsins are a group of serine, aspartic, and cysteine proteases, which contribute to vascular remodelling. Several cathepsins, including cathepsins A, D, S, K, and L are reported to be involved or upregulated in humans aortic aneurysmal tissues 100,101,118 . Cathepsin K and S are potent elastases that are produced by SMCs and macrophages in the aorta under inflammatory milieus.…”

Pathogenic mechanisms and the potential of drug therapies for aortic aneurysm

“…Cathepsins are a family of cysteine proteases that have been suggested to contribute to aneurysm onset and progression. Cathepsins A, D, K, L, and S are elevated in human AAA samples (62,118,244). Cathepsin K and S can be produced by SMCs and macrophages under inflammatory conditions and have strong elastinolytic activities (83,195,207).…”

The relationship between famine exposure in early life and ascending aorta dilatation in adulthood

“…Demir, et al [22] found that vitamin D de ciency was an independent factor for aortic dilatation. Adam and his team discovered the concentration of Copper and Zinc was signi cant associated with the size of the aneurysmal enlargement in the wall of the abdominal aortic aneurysm [23]. In addition, although there was no research has speci cally evaluated the relationship between Chinese early life famine exposure and AAD in adulthood, we further found that there was a stronger risk of AAD in female, BMI ≥ 24 kg/m 2 , smokers, hypertensive patients, and this effect has not been adjusted by the above traditional risk factors for AAD.…”