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Carbamylated LDL: the missing link between uremia and atherosclerosis
Author(s) -
Basnakian Alexei G.,
Apostolov Eugene O.,
Shah Sudhir V.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.116.5
Subject(s) - uremia , medicine , endocrinology , in vivo , lipoprotein , hemodialysis , cholesterol , biology , microbiology and biotechnology
Cardiovascular disease (CVD) due to atherosclerosis is an independent risk factor and the leading cause of death in uremic patients with chronic renal failure (CRF). Based on in vitro studies, carbamylated low‐density lipoprotein (cLDL), a product of LDL modification by urea‐derived cianate previously known as “uremic LDL,” has been recently recognized as a potential atherogenic factor induced by uremia. In this study, to determine the role of cLDL in atherogenesis in vivo , we used ApoE knockout mice fed with a high‐fat diet to induce elevation of LDL in blood plasma, while stable increase of plasma urea was achieved by surgically inducing CRF or increasing urea consumption supplied with drinking water. Our results showed that in both models, only mice on high‐fat diet with increased urea had elevated plasma cLDL, whereas oxidized LDL (oxLDL) remained unchanged. The cLDL increase was associated with aggravated atherosclerosis measured by intravital ultrasound echography and en face staining of lipid deposits in aorta, and cLDL was localized in the aortic wall. In a pilot study, CRF patients on hemodialysis were shown to have normal oxLDL and elevated cLDL that correlated with carotid atherosclerosis. This study is the first to demonstrate the role of cLDL in uremia‐induced atherosclerosis in vivo . The study was supported by NIH/NHLBI grant to A.G.B, and AHA grant to E.O.A.