Spontaneous and diet-aggravated hemolysis and its correction by probucol in SR-BI knockout mice with LDL-R deficiency.

Abstract

BACKGROUND:

High density lipoprotein receptor SR-BI plays a vital role in cholesterol homeostasis. Depletion of SR-BI causes plasma free cholesterol (FC) accumulation, which disrupts erythrocytes membrane and might induce hemolytic anemia. Here we explored the effects of hypercholesteremia, induced by depletion of low density lipoprotein receptor (LDL-R) and high fat diet (HFD) feeding, on plasma FC and possible hemolysis in SR-BI knockout (KO) mice, and the therapeutic effects of a lipid-lowering drug probucol.

METHODS AND RESULTS:

To determine the effects of LDL-R depletion, SR-BI KO mice were cross-bred with LDL-R KO mice to generate SR-BI/LDL-R double KO (dKO) mice. Compared to control wild type (WT), SR-BI KO and LDL-R KO mice fed normal chow diet (NCD), dKO mice fed NCD had increased plasma FC and developed macrocytic anemia, splenomegaly, jaundice and renal tubular hemosiderin deposition, indicating spontaneous hemolysis. To determine the effects of HFD feeding and probucol therapy, dKO and LDL-R KO mice were fed HFD containing 0.5% cholesterol and 20% fat with or without 1% probucol. HFD further increased plasma FC and aggravated hemolysis while probucol almost normalized plasma FC and corrected hemolysis in dKO mice.

CONCLUSION:

We demonstrated that in SR-BI KO mice, hypercholesteremia due to LDL-R deficiency significantly increased plasma FC and induced spontaneous hemolysis, which could be further exacerbated by HFD feeding. Probucol almost normalized plasma FC and corrected diet-aggravated hemolysis in SR-BI KO mice with LDL-R deficiency.

• Authors: Jiawei Liao, Mingming Gao, Mengyu Wang, Xin Guo, Wei Huang, George Liu
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) 2015 Jul 17-24 Vol. 463 Issue 1-2 Pg. 48-53 ISSN: 1090-2104 [Electronic] United States
• PMID: 25983325 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Anticholesteremic Agents
• Receptors, LDL
• Scarb1 protein, mouse
• Scavenger Receptors, Class B
• Hemosiderin
• Cholesterol
• Probucol

Topics

• Anemia, Macrocytic (blood, drug therapy, etiology)
• Animals
• Anticholesteremic Agents (pharmacology)
• Cholesterol (blood)
• Diet, High-Fat (adverse effects)
• Female
• Hemolysis (drug effects, physiology)
• Hemosiderin (metabolism)
• Hypercholesterolemia (blood, drug therapy, etiology)
• Kidney Tubules (drug effects, metabolism, pathology)
• Mice
• Mice, Knockout
• Probucol (pharmacology)
• Receptors, LDL (deficiency, genetics)
• Scavenger Receptors, Class B (deficiency, genetics)