Circulating CD36 is increased in hyperlipidemic mice: Cellular sources and triggers of release.

Circulating CD36 is increased in hyperlipidemic mice: Cellular sources and triggers of release.
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DOI:
10.1016/j.freeradbiomed.2021.03.004
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发表时间:
2021-05-20
影响因子:
7.4
通讯作者:
Podrez EA
Podrez EA
中科院分区:
医学1区
文献类型:
--
作者:
Biswas S;Gao D;Altemus JB;Rekhi UR;Chang E;Febbraio M;Byzova TV;Podrez EA

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CD 36是一种多功能跨膜糖蛋白,在多种细胞类型中大量表达。最近的研究已经确定了循环中的CD 36(cCD 36)在几种慢性炎症性疾病中,包括2型糖尿病和慢性肾脏疾病,并提出cCD 36是疾病活动的生物标志物。尚不清楚cCD 36是否存在于高脂血症(一种以氧化应激和低度炎症为特征的疾病)中。此外,cCD 36的细胞来源和CD 36释放的触发因素尚未阐明。我们现在证明,血浆cCD 36水平在高脂血症ApoE−/−和Ldlr−/−小鼠中升高。使用几种细胞特异性CD 36基因敲除小鼠,我们发现多种细胞类型有助于高血压条件下cCD 36的产生,其中内皮细胞的贡献特别大。体外研究表明,已知在高脂血症循环中蓄积的氧化磷脂(CD 36配体,oxPCCD 36)可诱导多种细胞类型中CD 36的稳健释放。体内研究已经证明,响应于尾静脉注射oxPC ⑶ 36,⑶ 36释放到WT小鼠的循环中。这些发现证明了cCD 36在高脂血症中的存在,并确定了cCD 36与氧化应激和高脂血症相关的低度炎症下产生的氧化磷脂之间的联系。
CD36 is a multifunctional transmembrane glycoprotein abundantly expressed in several cell types. Recent studies have identified CD36 in circulation (cCD36) in several chronic inflammatory diseases, including type 2 diabetes and chronic kidney disease, and proposed cCD36 to be a biomarker of disease activity. Whether cCD36 is present in hyperlipidemia, a condition characterized by oxidative stress and low-grade inflammation, is not known. In addition, the cellular origin of cCD36 and triggers of CD36 release have not been elucidated. We now demonstrate that plasma cCD36 level is increased in hyperlipidemic ApoE−/− and Ldlr−/− mice. Using several cell-specific CD36 knockout mice, we showed that multiple cell types contribute to cCD36 generation in hyperlipidemic conditions, with a particularly strong contribution from endothelial cells. In vitro studies have demonstrated that oxidized phospholipids, ligands for CD36 (oxPCCD36), which are known to accumulate in circulation in hyperlipidemia, induce a robust release of CD36 from several cell types. In vivo studies have demonstrated CD36 release into the circulation of WT mice in response to tail-vein injection of oxPCCD36. These findings document the presence of cCD36 in hyperlipidemia and identify a link between cCD36 and oxidized phospholipids generated under oxidative stress and low-grade inflammation associated with hyperlipidemia.
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