Accumulation of Carbamylation-Derived Products in Aneurysmal Aorta.

Abstract

Introduction: Carbamylation is a nonenzymatic post-translational modification of proteins characterized by the binding of isocyanic acid to amino groups of proteins, which leads to the alteration of their properties. An increase in serum carbamylation-derived products, including homocitrulline (HCit), has been shown to be associated with the development of cardiovascular diseases.

Methods: HCit was quantified by LC-MS/MS within extracts of aneurysmal and control human aortas. A mouse model of aortic aneurysm (ApoE-/- mice perfused with angiotensin II and fed with sodium cyanate) was used to evaluate the role of carbamylation in aneurysm development.

Results: HCit quantification showed a greater heterogeneity of values in aneurysmal aortas in comparison with control ones. At the maximum diameter of dilation, HCit values were significantly higher (+94%, p < 0.05) compared with less dilated areas. No differences were observed according to aneurysm size or when comparing ruptured and unruptured aneurysms. No significant effect of carbamylation on aneurysm development was observed using the animal model.

Conclusions: These results evidenced the accumulation of HCit within aneurysmal aortas but do not allow concluding about the exact participation of protein carbamylation in the development of human abdominal aortic aneurysms.