OBJECTIVE: In human abdominal aortic aneurysm, the accumulation of blood-derived cells and proteases within the mural thrombus plays a pivotal role in the evolution toward vessel wall rupture. We sought to identify peptides released from abdominal aortic aneurysm specimens, characterized by an intraluminal thrombus. METHODS AND RESULTS: Intraluminal thrombus samples were analyzed by differential proteomics, using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. A 1309-Da peptide was detected in larger amounts in the newly formed luminal thrombus layer relative to older layers. It was identified as being LVVYPWTQRF (known as LVV-Hemorphin 7), a peptide generated from hemoglobin by cathepsin D. By immunohistochemical analysis, we showed that Hemorphin 7 (H7) colocalizes with cathepsin D and cathepsin G in the luminal layer of the intraluminal thrombus. In vitro, cathepsin G was able to generate H7 peptides at pH 7.4, whereas cathepsin D was only active in acidic conditions. Finally, H7 peptides were shown to be increased 3- to 4-fold in sera of abdominal aortic aneurysm patients relative to controls, and their levels were positively correlated with the volume of the thrombus. CONCLUSIONS: Our results suggest that circulating H7 peptides may reflect proteolysis of hemoglobin in the aneurysmal intraluminal thrombus and may be used as a biological marker of pathological vascular remodeling.
OBJECTIVE: In humanabdominal aortic aneurysm, the accumulation of blood-derived cells and proteases within the mural thrombus plays a pivotal role in the evolution toward vessel wall rupture. We sought to identify peptides released from abdominal aortic aneurysm specimens, characterized by an intraluminal thrombus. METHODS AND RESULTS:Intraluminal thrombus samples were analyzed by differential proteomics, using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. A 1309-Da peptide was detected in larger amounts in the newly formed luminal thrombus layer relative to older layers. It was identified as being LVVYPWTQRF (known as LVV-Hemorphin 7), a peptide generated from hemoglobin by cathepsin D. By immunohistochemical analysis, we showed that Hemorphin 7 (H7) colocalizes with cathepsin D and cathepsin G in the luminal layer of the intraluminal thrombus. In vitro, cathepsin G was able to generate H7 peptides at pH 7.4, whereas cathepsin D was only active in acidic conditions. Finally, H7 peptides were shown to be increased 3- to 4-fold in sera of abdominal aortic aneurysmpatients relative to controls, and their levels were positively correlated with the volume of the thrombus. CONCLUSIONS: Our results suggest that circulating H7 peptides may reflect proteolysis of hemoglobin in the aneurysmal intraluminal thrombus and may be used as a biological marker of pathological vascular remodeling.
Authors: Roxana Martinez-Pinna; Coral Barbas; Luis Miguel Blanco-Colio; Jose Tunon; Priscila Ramos-Mozo; Juan Antonio Lopez; Olivier Meilhac; Jean-Baptiste Michel; Jesus Egido; José Luis Martin-Ventura Journal: Curr Atheroscler Rep Date: 2010-05 Impact factor: 5.113
Authors: Françoise Stanke-Labesque; Jean-Louis Pépin; Tiphaine de Jouvencel; Claire Arnaud; Jean-Philippe Baguet; Marcelo H Petri; Renaud Tamisier; Jean François Jourdil; Patrick Lévy; Magnus Bäck Journal: J Lipid Res Date: 2012-07-03 Impact factor: 5.922
Authors: Jing Wang; Galina K Sukhova; Jian Liu; Keith Ozaki; Adam Lesner; Peter Libby; Petri T Kovanen; Guo-Ping Shi Journal: J Vasc Surg Date: 2014-07-16 Impact factor: 4.268