title: Electronegative Low-density Lipoprotein Increases Coronary Artery Disease Risk in Uremia Patients on Maintenance Hemodialysis.
abstract: Electronegative low-density lipoprotein (LDL) is a recognized factor in the pathogenesis of coronary artery disease (CAD) in the general population, but its role in the development of CAD in uremia patients is unknown. L5 is the most electronegative subfraction of LDL isolated from human plasma. In this study, we examined the distribution of L5 (L5%) and its association with CAD risk in uremia patients.The LDL of 39 uremia patients on maintenance hemodialysis and 21 healthy controls was separated into 5 subfractions, L1-L5, with increasing electronegativity. We compared the distribution and composition of plasma L5 between uremia patients and controls, examined the association between plasma L5% and CAD risk in uremia patients, and studied the effects of L5 from uremia patients on endothelial function.Compared to controls, uremia patients had significantly increased L5% (P < 0.001) and L5 that was rich in apolipoprotein C3 and triglycerides. L5% was significantly higher in uremia patients with CAD (n = 10) than in those without CAD (n = 29) (P < 0.05). Independent of other major CAD risk factors, the adjusted odds ratio for CAD was 1.88 per percent increase in plasma L5% (95% CI, 1.01-3.53), with a near-linear dose-response relationship. Compared with controls, uremia patients had decreased flow-mediated vascular dilatation. In ex vivo studies with preconstricted rat thoracic aortic rings, L5 from uremia patients inhibited acetylcholine-induced relaxation. In cultured human endothelial cells, L5 inhibited endothelial nitric oxide synthase activation and induced endothelial dysfunction.Our findings suggest that elevated plasma L5% may induce endothelial dysfunction and play an important role in the increased risk of CAD in uremia patients.
authors.affiliation: From the L5 Research Center, China Medical University (CMU) Hospital (C-TC, J-YH, A-SL, C-MC, M-YS, C-YY, C-HC); Division of Nephrology, CMU Hospital (C-TC, C-CK, C-CH); College of Medicine, CMU (C-TC, C-CK); Graduate Institute of Clinical Medical Science, CMU (G-JW, C-CW, M-YS); Department of Health and Nutrition Biotechnology, Asia University (G-JW), Taichung, Taiwan; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA (C-CK); Department of Medicine, Mackay Medical College, New Taipei, Taiwan (A-SL); Department of Physiology, Shinshu University School of Medicine, Matsumoto, Nagono, Japan (TS); Vascular and Medicinal Research, Texas Heart Institute, Houston, Texas, USA (NS, C-HC); Lipid Science and Aging Research Center, Kaohsiung Medical University (KMU) (C-HC); Center for Lipid Biosciences, KMU Hospital, KMU, Kaohsiung (C-HC); New York Heart Research Foundation, Mineola, New York, USA (C-HC); and Lipid and Glycoimmune Research Center, Changhua Christian Hospital, Changhua, Taiwan (C-HC).
authors.forename: Chiz-Tzung
authors.initials: CT
authors.lastname: Chang
authors.forename: Guei-Jane
authors.initials: GJ
authors.lastname: Wang
authors.forename: Chin-Chi
authors.initials: CC
authors.lastname: Kuo
authors.forename: Ju-Yi
authors.initials: JY
authors.lastname: Hsieh
authors.forename: An-Sean
authors.initials: AS
authors.lastname: Lee
authors.forename: Chia-Ming
authors.initials: CM
authors.lastname: Chang
authors.forename: Chun-Cheng
authors.initials: CC
authors.lastname: Wang
authors.forename: Ming-Yi
authors.initials: MY
authors.lastname: Shen
authors.forename: Chiu-Ching
authors.initials: CC
authors.lastname: Huang
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Sawamura
authors.forename: Chao-Yuh
authors.initials: CY
authors.lastname: Yang
authors.forename: Nicole
authors.initials: N
authors.lastname: Stancel
authors.forename: Chu-Huang
authors.initials: CH
authors.lastname: Chen
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000097:blood* / Q000209:etiology; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D006435:Renal Dialysis; D012307:Risk Factors; D051127:Scavenger Receptors, Class E / Q000378:metabolism; D014511:Uremia / Q000097:blood* / Q000150:complications* / Q000628:therapy; D059289:Vascular Stiffness; D014664:Vasodilation
chemical_list: D008077:Lipoproteins, LDL; C495137:OLR1 protein, human; D051127:Scavenger Receptors, Class E; C099252:oxidized low density lipoprotein; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III