Electronegative low-density lipoprotein increases the risk of ischemic lower-extremity peripheral artery disease in uremia patients on maintenance hemodialysis

Sci Rep. 2017 Jul 5;7(1):4654. doi: 10.1038/s41598-017-04063-3.

Abstract

Electronegative low-density lipoprotein (LDL) has been shown to increase coronary artery disease risk in hemodialysis patients, but its effect on the risk of peripheral artery disease (PAD) remains unclear. We separated plasma LDL from 90 uremia patients undergoing hemodialysis into 5 subfractions (L1-L5) according to charge by using fast-protein liquid chromatography with an anion-exchange column and examined the distribution of L5-the most electronegative LDL subfraction-in total LDL (i.e. L5%). During a 5-year period, we followed up with these patients until the occurrence of ischemic lower-extremity PAD. During the follow-up period, ischemic lower-extremity PAD developed in 24.4% of hemodialysis patients. L5% was higher in hemodialysis patients in whom ischemic lower-extremity PAD occurred (3.03% [IQR, 2.36-4.54], n = 22) than in hemodialysis patients in whom PAD did not occur (1.13% [IQR, 0.90-1.83], n = 68) (p < 0.001). Furthermore, L5% significantly increased the adjusted hazard ratio of ischemic lower-extremity PAD (1.54 [95% CI, 1.14-2.10]) (p = 0.005). Flow-mediated dilation was negatively associated with L5% (p < 0.001). Additionally, in vivo experiments from mice showed that L5 compromised endothelium-dependent vascular relaxation through a nitric oxide-related mechanism. Our findings indicate that increased L5% may be associated with the occurrence of ischemic lower-extremity PAD in hemodialysis patients.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromatography, Ion Exchange
  • Disease Models, Animal
  • Female
  • Humans
  • Ischemia / epidemiology*
  • Ischemia / etiology
  • Lipoproteins, LDL / adverse effects
  • Lipoproteins, LDL / blood*
  • Lower Extremity / blood supply*
  • Male
  • Mice
  • Middle Aged
  • Myocardial Ischemia
  • Peripheral Arterial Disease / epidemiology*
  • Peripheral Arterial Disease / etiology
  • Renal Dialysis
  • Uremia / blood
  • Uremia / metabolism
  • Uremia / therapy*

Substances

  • Lipoproteins, LDL
  • oxidized low density lipoprotein