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        Quantitative expression and localization of cysteine and aspartic proteases in human abdominal aortic aneurysms

        Fabian Lohoefer,Christian Reeps,Christina Lipp,Martina Rudelius,Felix Haertl,Edouard Matevossian,Alma Zernecke,Hans-Henning Eckstein,Jaroslav Pelisek 생화학분자생물학회 2014 Experimental and molecular medicine Vol.46 No.-

        Cysteine and aspartic proteases possess high elastolytic activity and might contribute to the degradation of the abdominal aortic aneurysm (AAA) wall. The aim of this study was to analyze, in detail, the proteases (cathepsins B, D, K, L and S, and inhibitor cystatin C) found in human AAA and healthy aortic tissue samples. The vessel walls from AAA patients (n¼36) and nonaneurysmal aortae (n¼10) were retrieved using conventional surgical repair and autopsy methods. Serum samples from the same AAA patients and 10 healthy volunteers were also collected. Quantitative expression analyses were performed at the mRNA level using real-time reverse transcriptase-PCR (RT–PCR). Furthermore, analyses at the protein level included western blot and immunoprecipitation analyses. Cellular sources of cysteine/aspartic proteases and cystatin C were identified by immunohistochemistry (IHC). All cysteine/aspartic proteases and cystatin C were detected in the AAA and control samples.Using quantitative RT–PCR, a significant increase in expression was observed for cathepsins B (P¼0.021) and L (P¼0.018),compared with the controls. Cathepsin B and cystatin C were also detected in the serum of AAA patients. Using IHC, smooth muscle cells (SMCs) and macrophages were positive for all of the tested cathepsins, as well as cystatin C; in addition, the lymphocytes were mainly positive for cathepsin B, followed by cathepsins D and S. All cysteine/aspartic proteases analyzed in our study were detected in the AAA and healthy aorta. The highest expression was found in macrophages and SMCs. Consequently, cysteine/aspartic proteases might play a substantial role in AAA.

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        Graft Preconditioning with Low-dose Tacrolimus (FK506) and Nitric Oxide Inhibitor Aminoguanidine (AGH) Reduces Ischemia/ reperfusion Injury after Liver Transplantation in the Rat

        Norbert Hüser,Dietrich Doll,Jennifer Altomonte,Martin Werner,Monika Kriner,Anne Preissel,Stefan Thorban,Edouard Matevossian 대한약학회 2009 Archives of Pharmacal Research Vol.32 No.2

        Ischemia/reperfusion (I/R) injury is a main cause of primary dysfunction or non-function after liver transplantation (LTx). Recent evidence indicates that an increase in nitric oxide (NO) production after LTx is associated with I/R injury. The aim of this study was to demonstrate that low-dose FK506 in combination with aminoguanidine (AGH), which leads to a reduction of NO levels, has a protective effect by reducing I/R associated injury after LTx. Fortyone DA-(RT1av1) rats served as donors and recipients for syngenic orthotopic arterialised LTx. They were divided into 4 groups: controls without pre-/treatment (I), pre-/treatment with high-dose FK506 (II), pre-/treatment with AGH only (Ⅲ), and pre-/treatment with low-dose FK506 in combination with AGH (Ⅳ). After LTx the laboratory parameters and liver biopsy were performed. The levels of transaminase (ALT) in groups I, II and III were significantly higher on day 3 after LTx compared to group Ⅳ (p = 0.001, p = 0.001, p = 0.000). In group Ⅳ the I/R-associated liver necrosis rate was reduced significantly. Our results demonstrated that a combined dual pharmacological pretreatment (group Ⅳ) reduced I/R injury of the graft after LTx in a rat model.

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