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.

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 enzyme-linked 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. Mann-Whitney 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 = 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.

Different effects of commonly prescribed statins on abdominal aortic aneurysm wall biology.

BACKGROUND: Pharmaceutical stabilisation of the abdominal aortic aneurysm (AAA) wall can delay surgery and improve outcome. Observational studies indicate statins can be used to reduce AAA growth but mechanistic data are scarce. In this study, our aim was to determine the pleiotropic effects of different statins on AAA wall composition. METHODS: We included 216 patients undergoing open AAA repair, of which 60 used simvastatin, 52 atorvastatin and 23 pravastatin. The AAA wall histology and protein expression (IL 1beta,2,4,5,6,8,10,12, interferon-gamma (IFNgamma), tumour necrosis factor (TNF)alpha,beta, matrix metalloproteinase (MMP)2 and 9 activities, total MMP8,9 and cathepsin A and B levels) between statin users and non-users were compared as also among the use of different statins. RESULTS: As far as histological inflammation goes, the AAA walls of statin users did not differ from those not using them. After multivariate adjustment for risk factors, pravastatin use was associated with tendencies of increased MMP8 (p = 0.022), active MMP9 (p = 0.040) and higher cathepsin B (p = 0.056) levels. The AAA walls of simvastatin and atorvastatin users showed no differences in proteases or cytokines in multivariate analyses. CONCLUSIONS: The use of statins was not associated with a decrease in protease levels or inflammation. The trends of elevated protease levels associated with pravastatin use suggest pleiotropic differences among the various statins, supporting the need for further research to target pharmaceutical AAA treatment.

Monitoring the neuropeptide metabolites by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

The developments of bio-analytical methods for analyzing bioactive peptides are of paramount importance. Neuropeptides and their bioactive fragments play a vital role in the regulation of many biological processes and diseases. This paper presents the use of matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometry (MS) method for monitoring neuropeptides along with their degradation products in plasma samples from cancer patients. The neuropeptides focused in this study were beta-endrophin, substance P, and bradykinin. The method involves the enzyme digestion of the neuroactive peptides followed by MALDI-MS sample preparation and subsequent acquisition of the MS spectral data. The mass spectral profile identifies most of the C-terminal and N-terminal peptides, and the mass accuracy was in the range of -1.68 to 1.46 Da with the mass spectrometer utilised. Analysis of the neuropeptide degradation patterns from the cancer patients were compared with the controls showed similar results. The study reveals that this approach can be used to identify the enzymatic digestion products of protein.

Inhibition of CatA: an emerging strategy for the treatment of heart failure.

The lysosomal serine carboxypeptidase CatA has a very important and well-known structural function as well as a, so far, less explored catalytic function. A complete loss of the CatA protein results in the lysosomal storage disease galactosialidosis caused by intralysosomal degradation of ß-galactosidase and neuraminidase 1. However, mice with a catalytically inactive CatA enzyme show no signs of this disease. This observation establishes a clear distinction between structural and catalytic functions of the CatA enzyme. Recently, several classes of orally bioavailable synthetic inhibitors of CatA have been identified. Pharmacological studies in rodents indicate a remarkable influence of CatA inhibition on cardiovascular disease progression and identify CatA as a promising novel target for the treatment of heart failure.