Vitamin A Decreases Cytotoxicity of Oxidized Low-Density Lipoprotein in Patients with Atherosclerosis

Immunol Invest. 2016;45(1):52-62. doi: 10.3109/08820139.2015.1095208. Epub 2015 Dec 23.

Abstract

Background: Oxidized low-density lipoprotein (ox-LDL) is implicated in initiation and progression of atherosclerosis. Previously, we found that ox-LDL increases vulnerability of peripheral blood mononuclear cells (PBMCs) in atherosclerotic patients compared to controls. Vitamin A induces proliferation of PBMCs. The aim of this study was to determine the effect of vitamin A supplementation on PBMC survival against LDL and different doses of ox-LDL.

Method: In this double-blind placebo-controlled trial, we recruited 35 atherosclerotic patients and 38 healthy controls and randomly allocated them into placebo and vitamin A groups, which received either placebo or 25,000 IU/day of vitamin A for 3 months. PBMCs were isolated, cultured, and stimulated by 1 µg/mL LDL as well as 1 µg/mL and 50 µg/mL ox-LDL. The stimulation indexes (SIs) of PBMCs were calculated to identify cell viability. Additionally, the circulating ox-LDL levels were measured by ELISA.

Results: Viability of PBMCs stimulated by 50 µg/mL ox-LDL significantly increased following vitamin A supplementation in patients (p < 0.01). The levels of circulating ox-LDL were not changed by vitamin A treatment. Ox-LDL levels were strongly and positively correlated to SI of PBMCs stimulated by 1 µg/mL LDL and1 µg/mL ox-LDL in all groups.

Conclusion: Vitamin A decreases cytotoxicity of high-dose ox-LDL and improves PBMC viability. The protective effect of vitamin A is not mediated by an antioxidative mechanism, but may instead have been due to intracellular protection of the apoptotic machinery or induction of proliferation of the cells. Higher levels of ox-LDL increase PBMC irritability in all participants.

Keywords: Atherosclerosis; cell viability; cytotoxicity; oxidized LDL; peripheral blood mononuclear cells; vitamin A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Atherosclerosis / metabolism*
  • Case-Control Studies
  • Cell Survival / drug effects
  • Comorbidity
  • Humans
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Lipoproteins, LDL / metabolism*
  • Lipoproteins, LDL / toxicity
  • Middle Aged
  • Risk Factors
  • Vitamin A / metabolism*
  • Vitamin A / pharmacology

Substances

  • Lipoproteins, LDL
  • oxidized low density lipoprotein
  • Vitamin A