Reduction of endoplasmic reticulum stress--a novel mechanism of action of statins in the protection against atherosclerosis

Ikaro Breder; Andressa Coope; Ana Paula Arruda; Daniela Razolli; Marciane Milanski; Gabriel de Gabriel Dorighello; Helena C F de Oliveira; Lício A Velloso

doi:10.1016/j.atherosclerosis.2010.04.036

Reduction of endoplasmic reticulum stress--a novel mechanism of action of statins in the protection against atherosclerosis

Atherosclerosis. 2010 Sep;212(1):30-1. doi: 10.1016/j.atherosclerosis.2010.04.036. Epub 2010 May 6.

Authors

Ikaro Breder, Andressa Coope, Ana Paula Arruda, Daniela Razolli, Marciane Milanski, Gabriel de Gabriel Dorighello, Helena C F de Oliveira, Lício A Velloso

PMID: 20537647
DOI: 10.1016/j.atherosclerosis.2010.04.036

Abstract

Fatty-acid-induced endoplasmic reticulum stress has been recently described as a novel mechanism involved in the genesis of atherosclerosis. Here we show that statins, a class of drug widely employed in the clinical management of hypercholesterolemia, reduces lipid-induced macrophage endoplasmic reticulum stress in an isolated cell system and in LDL receptor knockout mice. Given the importance of endoplasmic reticulum stress as an inducer of inflammation, we suspect that the novel mechanism of action herein described for statins may play a major role on its beneficial effects in the prevention of cardiovascular disease.

Publication types

Letter
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antigens, Differentiation / metabolism
Atherosclerosis / drug therapy*
Atherosclerosis / genetics
Atherosclerosis / metabolism
Cell Line
DNA-Binding Proteins / metabolism
Disease Models, Animal
Endoplasmic Reticulum / drug effects*
Endoplasmic Reticulum / metabolism
Endoplasmic Reticulum Chaperone BiP
Eukaryotic Initiation Factor-2 / metabolism
Fatty Acids / metabolism*
Heat-Shock Proteins / metabolism
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
Macrophages / drug effects*
Macrophages / metabolism
Mice
Mice, Knockout
Phosphorylation
Pravastatin / pharmacology
Receptors, LDL / deficiency
Receptors, LDL / genetics
Regulatory Factor X Transcription Factors
Simvastatin / pharmacology
Stress, Physiological / drug effects*
Transcription Factors / metabolism
eIF-2 Kinase / metabolism

Substances

Antigens, Differentiation
DNA-Binding Proteins
Endoplasmic Reticulum Chaperone BiP
Eukaryotic Initiation Factor-2
Fatty Acids
Heat-Shock Proteins
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Receptors, LDL
Regulatory Factor X Transcription Factors
Transcription Factors
monocyte-macrophage differentiation antigen
Simvastatin
PERK kinase
eIF-2 Kinase
Pravastatin