Pirillo A, Zhu W, Roma P, Galli G, Caruso D, Pellegatta F, Catapano A L
Institute of Pharmacological Sciences, University of Milano, Via Balzaretti 9, 20133, Milano, Italy.
FEBS Lett. 1999 Nov 26;462(1-2):113-6. doi: 10.1016/s0014-5793(99)01497-0.
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.
氧化型低密度脂蛋白（OxLDL）具有多种促动脉粥样硬化特性，其中显著的细胞毒性最为突出。在体外，OxLDL对内皮细胞的细胞毒性与诱导型热休克蛋白70（hsp70）表达增加有关，hsp70通常被视为一种细胞保护蛋白。LDL氧化后形成的胆固醇氧化衍生物具有细胞毒性。此外，OxLDL的大部分细胞毒性归因于其脂质部分，尤其是氧化甾醇。在本报告中，我们证明尽管在OxLDL中鉴定出的氧化甾醇具有细胞毒性，但它们无法引发完整氧化脂蛋白所观察到的hsp70表达增加。因此，我们推测氧化甾醇可能代表LDL中氧化脂质的最具毒性的形式，因为它们无法激活一种挽救机制（即hsp反应），并且可能对动脉粥样硬化斑块内的细胞死亡有显著贡献。
