Deletion of soluble epoxide hydrolase suppressed chronic kidney disease-related vascular calcification by restoring Sirtuin 3 expression.
Deletion of soluble epoxide hydrolase suppressed chronic kidney disease-related vascular calcification by restoring Sirtuin 3 expression.
复制标题
可溶性环氧化物水解酶的缺失通过恢复 Sirtuin 3 的表达来抑制慢性肾病相关的血管钙化
DOI：
10.1038/s41419-021-04283-6
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发表时间：
2021-10-23
影响因子：
9
通讯作者：
Huang H
中科院分区：
文献类型：
--
作者：
He W;Huang J;Liu Y;Xie C;Zhang K;Zhu X;Chen J;Huang H
血管钙化在慢性肾脏疾病（CKD）中很常见，并导致心血管疾病（CVD），迄今为止没有任何有效的治疗方法。可溶性环氧化物水解酶（sEH）在有无血管钙化患者中的表达不同。本研究探讨了sEH作为CKD血管钙化潜在介质的作用。Ephx 2 −/−和野生型（WT）小鼠均喂食高腺嘌呤和磷酸盐（AP）饮食，以探索CKD中的血管钙化。与WT相比，sEH的缺失抑制AP诱导的血管钙化。sEH的缺失也消除了高磷（Pi）诱导的血管平滑肌细胞（VSMCs）的表型转变，而不依赖于其环氧二十碳三烯酸（E3）的水解。进一步的基因表达分析确定了Sirtuin 3（Sirt 3）在sEH调节的VSMC钙化中的潜在作用。在高磷条件下，sEH与Sirt 3相互作用，使Sirt 3失稳，加速了Sirt 3的降解。sEH的缺失可保护Sirt 3的表达，从而维持线粒体三磷酸腺苷（adenosine triphosphate，ATP）的合成和形态，显著抑制VSMC钙化。我们的数据支持sEH缺失抑制血管钙化，并表明sEH抑制在血管钙化预防中有希望的靶点。
Vascular calcification is common in chronic kidney disease (CKD) and contributes to cardiovascular disease (CVD) without any effective therapies available up to date. The expression of soluble epoxide hydrolase (sEH) is different in patients with and without vascular calcification. The present study investigates the role of sEH as a potential mediator of vascular calcification in CKD. Both Ephx2−/−and wild-type (WT) mice fed with high adenine and phosphate (AP) diet were used to explore the vascular calcification in CKD. Compared with WT, deletion of sEH inhibited vascular calcification induced by AP. sEH deletion also abolished high phosphorus (Pi)-induced phenotypic transition of vascular smooth muscle cells (VSMCs) independent of its epoxyeicosatrienoic acids (EETs) hydrolysis. Further gene expression analysis identified the potential role of Sirtuin 3 (Sirt3) in the sEH-regulated VSMC calcification. Under high Pi treatment, sEH interacted with Sirt3, which might destabilize Sirt3 and accelerate the degradation of Sirt3. Deletion of sEH may preserve the expression of Sirt3, and thus maintain the mitochondrial adenosine triphosphate (ATP) synthesis and morphology, significantly suppressing VSMC calcification. Our data supported that sEH deletion inhibited vascular calcification and indicated a promising target of sEH inhibition in vascular calcification prevention.
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发表时间：
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影响因子：
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