Hemorphin 7 reflects hemoglobin proteolysis in abdominal aortic aneurysm.
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.
Dejouvencel
Tiphaine
T
Inserm, U698, Paris, France, Univ Paris 7, Paris, France.
Féron
Delphine
D
Rossignol
Patrick
P
Sapoval
Marc
M
Kauffmann
Claude
C
Piot
Jean-Marie
JM
Michel
Jean-Baptiste
JB
Fruitier-Arnaudin
Ingrid
I
Meilhac
Olivier
O
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
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