Oxysterols from oxidized LDL are cytotoxic but fail to induce hsp70 expression in endothelial cells.
Oxidized low density lipoprotein (OxLDL) possesses several proatherogenic characteristics, among which a marked cytotoxicity. In vitro, cytotoxicity of OxLDL to endothelial cells is associated with an increase in the expression of the inducible form of heat shock protein 70 (hsp70), generally regarded as a cytoprotective protein. Oxidized derivatives of cholesterol which form upon LDL oxidation are cytotoxic. Moreover, most of the OxLDL cytotoxicity is due to its lipid moiety, in particular to oxysterols. In this report we demonstrate that although oxysterols identified in OxLDL are cytotoxic, they cannot trigger the increase in hsp70 expression observed with intact oxidized lipoproteins. We speculate therefore that oxysterols may represent the most toxic form of oxidized lipids in LDL because they cannot activate a rescue mechanism (i.e. the hsp response) and may contribute significantly to cell death within atherosclerotic plaques.
Pirillo
A
A
Institute of Pharmacological Sciences, University of Milano, Via Balzaretti 9, 20133, Milano, Italy.
Zhu
W
W
Roma
P
P
Galli
G
G
Caruso
D
D
Pellegatta
F
F
Catapano
A L
AL
D017209:Apoptosis; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D015870:Gene Expression; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D006888:Hydroxycholesterols / Q000378:metabolism; D066298:In Vitro Techniques; D007653:Ketocholesterols / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D010084:Oxidation-Reduction
D018840:HSP70 Heat-Shock Proteins; D006888:Hydroxycholesterols; D007653:Ketocholesterols; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; C003001:7-ketocholesterol