Vitamin A decreases cytotoxicity of oxidized low-density lipoprotein in patients with atherosclerosis

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. © 2015 Taylor & Francis