- Meeting abstract
- Open Access
The effect of carbamylation on the functionality of high-density lipoprotein
© Holzer et al; licensee BioMed Central Ltd. 2009
- Published: 12 November 2009
- Atherosclerotic Plaque
- Atherosclerotic Lesion
- Lysine Residue
- Relative Functionality
Increasing interest has focused on the relative functionality of high-density lipoprotein (HDL), highlighted by observations that cardiovascular events can occur even in the presence of high levels of HDL cholesterol. Myeloperoxidase (MPO), a heme protein abundant in leucocytes, colocalizes with HDL in the human artery wall and has emerged as a potential participant in multiple phases of the atherosclerotic process. Recently, the MPO/H2O2/SCN- system has been demonstrated as a dominant pathway to promote protein carbamylation within atherosclerotic plaques. Therefore, we determined whether HDL is carbamylated in the human artery wall.
Immunohistochemical studies confirmed colocalization of carbamylated epitopes with apoA-I and macrophages in human atherosclerotic lesions. We performed shotgun proteomic analysis of in vitro carbamylated HDL to identify specific carbamylation sites of apoA-I. We could identify apoA-I-associated lysine residues in the α-helical lipid binding domains that are specifically carbamylated, indicating that carbamylation of apoA-I affects the functional integrity of HDL. In line with this observation, we observed that carbamylation of HDL (i) leads to "non-productive" binding to the HDL receptor (SR-BI), (ii) decreased SR-BI-mediated cholesterol efflux, and (iii) reduced HDL mediated anti-inflammatory activity.
Taken together, our data provide strong evidence that carbamylation renders HDL dysfunctional and proinflammatory.
This article is published under license to BioMed Central Ltd.