Hemorphin 7 Reflects Hemoglobin Proteolysis in Abdominal Aortic Aneurysm

作者：Dejouvencel Tiphaine; Feron Delphine; Rossignol Patrick; Sapoval Marc; Kauffmann Claude; Piot Jean Marie; Michel Jean Baptiste; Fruitier Arnaudin Ingrid; Meilhac Olivier^*

来源：Arteriosclerosis, Thrombosis, and Vascular Biology, 2010, 30(2): 269-U273.

DOI：10.1161/ATVBAHA.109.198309

• Human atherothrombosis
• cathepsin G
• cathepsin D
• circulating biomarker
• thrombus

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.
Conclusion-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. (Arterioscler Thromb Vasc Biol. 2010;30:269-275.)

• 出版日期2010-2