Atherosclerosis (AS) is the basis of cardiovascular diseases, characterized by chronic inflammatory and lipid metabolism disorders. Although the anti-inflammatory effect of Klotho in AS has been clearly shown, its lipid-lowering effect is unclear. In this study, we examined the effects of recombinant Klotho (Re-KL) protein on lipid accumulation in foam cells. THP-1 cells were exposed to 100 nM phorbol myristate acetate for 24 h and then to oxidized low-density lipoprotein (ox-LDL; 80 mg/mL) to induce foam cell formation. Subsequently, the foam cells were incubated with Re-KL and/or DKK1, an inhibitor of the Wnt/β-catenin pathway. Oil red O staining and cholesterol intake assay revealed that the foam cell model was constructed successfully. Pre-treatment of the foam cells with Re-KL decreased total cholesterol level, up-regulated the expression of ATP binding cassette transporter A1 (ABCA1) and G1 (ABCG1), and down-regulated the expression of acyl coenzyme a-cholesterol acyltransferase 1 (ACAT1) and members of the scavenger family (SR-A1 and CD36). In addition, the expression of Wnt/β-catenin pathway-related proteins in foam cells was significantly decreased by the stimulus of Re-KL. Interestingly, the effect of Re-KL was similar to that of DKK1 on foam cells. The Re-KL-induced up-regulation of reverse cholesterol transport capacity promotes cholesterol efflux and reduces lipid accumulation by suppressing the Wnt/β-catenin pathway in foam cells.

中文翻译：

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重组Klotho蛋白通过抑制Wnt /β-catenin信号通路增强THP-1巨噬细胞源性泡沫细胞的胆固醇外流

动脉粥样硬化（AS）是心血管疾病的基础，其特征在于慢性炎症和脂质代谢紊乱。尽管已经清楚地表明了Klotho在AS中的抗炎作用，但是其降脂作用尚不清楚。在这项研究中，我们检查了重组Klotho（Re-KL）蛋白对泡沫细胞脂质积累的影响。将THP-1细胞暴露于100 nM佛波醇肉豆蔻酸酯乙酸中24小时，然后暴露于氧化的低密度脂蛋白（ox-LDL; 80 mg / mL），以诱导泡沫细胞形成。随后，将泡沫细胞与Wnt /β-catenin途径的抑制剂Re-KL和/或DKK1孵育。油红O染色和胆固醇摄入测定表明泡沫细胞模型已成功构建。用Re-KL预处理泡沫细胞可降低总胆固醇水平，上调ATP结合盒转运蛋白A1（ABCA1）和G1（ABCG1）的表达，并下调酰基辅酶α-胆固醇酰基转移酶1（ACAT1）和清除剂家族成员（SR-A1和CD36）的表达。另外，Re-KL刺激可明显降低泡沫细胞中Wnt /β-catenin途径相关蛋白的表达。有趣的是，Re-KL对泡沫细胞的作用类似于DKK1。Re-KL诱导的逆胆固醇转运能力的上调通过抑制泡沫细胞中的Wnt /β-catenin途径促进胆固醇外排并减少脂质蓄积。Re-KL刺激可明显降低泡沫细胞中Wnt /β-catenin途径相关蛋白的表达。有趣的是，Re-KL对泡沫细胞的作用类似于DKK1。Re-KL诱导的逆胆固醇转运能力的上调通过抑制泡沫细胞中的Wnt /β-catenin途径促进胆固醇外排并减少脂质蓄积。Re-KL刺激可显着降低泡沫细胞中Wnt /β-catenin途径相关蛋白的表达。有趣的是，Re-KL对泡沫细胞的作用类似于DKK1。Re-KL诱导的逆胆固醇转运能力的上调通过抑制泡沫细胞中的Wnt /β-catenin途径促进胆固醇外排并减少脂质蓄积。