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.

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.

• Authors: Tiphaine Dejouvencel, Delphine Féron, Patrick Rossignol, Marc Sapoval, Claude Kauffmann, Jean-Marie Piot, Jean-Baptiste Michel, Ingrid Fruitier-Arnaudin, Olivier Meilhac
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 30 Issue 2 Pg. 269-75 (Feb 2010) ISSN: 1524-4636 [Electronic] United States
• PMID: 19910633 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Hemoglobins
• Peptide Fragments
• hemorphin 7
• LVV-hemorphin-7
• CTSG protein, human
• Cathepsin G
• CTSD protein, human
• Cathepsin D

Topics

• Aortic Aneurysm, Abdominal (enzymology, metabolism)
• Biomarkers (metabolism)
• Case-Control Studies
• Cathepsin D (metabolism)
• Cathepsin G (metabolism)
• Hemoglobins (metabolism)
• Humans
• Hydrogen-Ion Concentration
• Immunohistochemistry
• Peptide Fragments (blood, metabolism)
• Proteomics (methods)
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
• Thrombosis (enzymology, metabolism)
• Tissue Culture Techniques
• Up-Regulation