Quantitative expression and localization of cysteine and aspartic proteases in human abdominal aortic aneurysms.
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 (n=36) and nonaneurysmal aortae (n=10) 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 (P=0.021) and L (P=0.018), 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.
Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar der Technischen Universitaet Muenchen, Munich, Germany.
Fabian
F
Lohoefer
Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar der Technischen Universitaet Muenchen, Munich, Germany.
Christian
C
Reeps
Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar der Technischen Universitaet Muenchen, Munich, Germany.
Christina
C
Lipp
Institute of Pathology, Klinikum rechts der Isar der Technischen Universitaet Muenchen, Munich, Germany.
Martina
M
Rudelius
Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar der Technischen Universitaet Muenchen, Munich, Germany.
Felix
F
Haertl
Department of Surgery, Klinikum rechts der Isar der Technischen Universitaet Muenchen, Munich, Germany.
Edouard
E
Matevossian
Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar der Technischen Universitaet Muenchen, Munich, Germany.
Alma
A
Zernecke
Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar der Technischen Universitaet Muenchen, Munich, Germany.
Hans-Henning
HH
Eckstein
Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar der Technischen Universitaet Muenchen, Munich, Germany.
Jaroslav
J
Pelisek
D000368:Aged; D001011:Aorta / Q000201:enzymology; D017544:Aortic Aneurysm, Abdominal / Q000201:enzymology*; D057055:Aspartic Acid Proteases / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D002403:Cathepsins / Q000235:genetics / Q000378:metabolism; D057056:Cysteine Proteases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008214:Lymphocytes / Q000201:enzymology; D008264:Macrophages / Q000201:enzymology; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000201:enzymology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D057055:Aspartic Acid Proteases; D002403:Cathepsins; D057056:Cysteine Proteases