title: Hemorphin 7 reflects hemoglobin proteolysis in abdominal aortic aneurysm.
abstract: 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.
  
  
  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.
authors.affiliation: Inserm, U698, Paris, France, Univ Paris 7, Paris, France.
authors.forename: Tiphaine
authors.initials: T
authors.lastname: Dejouvencel
authors.forename: Delphine
authors.initials: D
authors.lastname: Féron
authors.forename: Patrick
authors.initials: P
authors.lastname: Rossignol
authors.forename: Marc
authors.initials: M
authors.lastname: Sapoval
authors.forename: Claude
authors.initials: C
authors.lastname: Kauffmann
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Piot
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Michel
authors.forename: Ingrid
authors.initials: I
authors.lastname: Fruitier-Arnaudin
authors.forename: Olivier
authors.initials: O
authors.lastname: Meilhac
mesh_terms: D017544:Aortic Aneurysm, Abdominal / Q000201:enzymology / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D002402:Cathepsin D / Q000378:metabolism*; D056649:Cathepsin G / Q000378:metabolism*; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D010446:Peptide Fragments / Q000097:blood / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013927:Thrombosis / Q000201:enzymology / Q000378:metabolism*; D046509:Tissue Culture Techniques; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D006454:Hemoglobins; D010446:Peptide Fragments; C085122:hemorphin 7; C074309:LVV-hemorphin-7; C534094:CTSG protein, human; D056649:Cathepsin G; C533922:CTSD protein, human; D002402:Cathepsin D