Reduction of endoplasmic reticulum stress--a novel mechanism of action of statins in the protection against atherosclerosis.
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.
Ikaro
I
Breder
Andressa
A
Coope
Ana Paula
AP
Arruda
Daniela
D
Razolli
Marciane
M
Milanski
Gabriel de Gabriel
Gde G
Dorighello
Helena C F
HC
de Oliveira
Lício A
LA
Velloso
D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D050197:Atherosclerosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D017035:Pravastatin / Q000494:pharmacology; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics; D000071701:Regulatory Factor X Transcription Factors; D019821:Simvastatin / Q000494:pharmacology; D013312:Stress, Physiological / Q000187:drug effects*; D014157:Transcription Factors / Q000378:metabolism; D019892:eIF-2 Kinase / Q000378:metabolism
D000943:Antigens, Differentiation; D004268:DNA-Binding Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D015852:Eukaryotic Initiation Factor-2; D005227:Fatty Acids; D006360:Heat-Shock Proteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017035:Pravastatin; D011973:Receptors, LDL; D000071701:Regulatory Factor X Transcription Factors; D019821:Simvastatin; D014157:Transcription Factors; D019892:eIF-2 Kinase; C036763:monocyte-macrophage differentiation antigen