Department of Gerontology, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, China.
BMC Cardiovasc Disord. 2020 Mar 5;20(1):120. doi: 10.1186/s12872-020-01400-9.
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.
动脉粥样硬化（AS）是心血管疾病的基础，其特征为慢性炎症和脂质代谢紊乱。虽然 Klotho 在 AS 中的抗炎作用已得到明确证实，但它的降脂作用尚不清楚。在本研究中，我们研究了重组 Klotho（Re-KL）蛋白对泡沫细胞脂质积累的影响。
THP-1 细胞用 100 nM 佛波醇肉豆蔻酸酯（PMA）孵育 24 小时，然后用氧化低密度脂蛋白（ox-LDL；80 mg/mL）诱导泡沫细胞形成。随后，用 Re-KL 和/或 Wnt/β-catenin 通路抑制剂 DKK1 孵育泡沫细胞。
油红 O 染色和胆固醇摄取试验表明成功构建了泡沫细胞模型。Re-KL 预处理泡沫细胞可降低总胆固醇水平，上调三磷酸腺苷结合盒转运体 A1（ABCA1）和 G1（ABCG1）的表达，下调酰基辅酶 A-胆固醇酰基转移酶 1（ACAT1）和清道夫受体家族（SR-A1 和 CD36）成员的表达。此外，Re-KL 刺激显著降低了泡沫细胞中 Wnt/β-catenin 通路相关蛋白的表达。有趣的是，Re-KL 的作用与 DKK1 对泡沫细胞的作用相似。
Re-KL 诱导的胆固醇逆转运能力增强通过抑制泡沫细胞中的 Wnt/β-catenin 通路促进胆固醇外排和减少脂质积累。
