小柯机器人

美国哈佛医学院Chad A. Cowan、Takafumi Toyohara等研究人员合作利用病人来源的诱导多能干细胞发现，血管平滑肌芳基乙酰胺脱乙酰基酶可预防动脉粥样硬化。相关论文于2020年5月14日在线发表在《细胞—干细胞》杂志上。

研究人员表示，尽管每个患者对心血管疾病（CVD）的敏感性均不同，但是尚不清楚为何某些2型糖尿病（T2DM）患者发展为CVD而其他患者却没有。

使用T2DM患者来源的人诱导多能干细胞（hiPSC），研究人员发现在患有CVD的患者中，血管平滑肌细胞（VSMC）中一种酯酶——芳基乙酰胺脱乙酰基酶（AADAC）的表达明显升高。研究人员在人类原代VSMC和与hiPSC分化的VSMC中过表达了这种酯酶，并观察到脂滴的数量显著减少。

进一步的代谢组学分析表明，脂质的存储量显著减少、膜磷脂增加，这表明脂质生物装配的肯尼迪途径（Kennedy pathway）发生了变化。在过表达AADAC的VSMC中，细胞迁移和增殖也显著降低。此外，在载脂蛋白E（Apoe）敲除小鼠中过表达VSMC特异性Aadac能够改善动脉粥样硬化病变。这些发现表明，VSMC中较高的AADAC表达可保护T2DM患者免于CVD。

附：英文原文

Title: Patient hiPSCs Identify Vascular Smooth Muscle Arylacetamide Deacetylase as Protective against Atherosclerosis

Author: Takafumi Toyohara, Filip Roudnicky, Mary H.C. Florido, Toshiaki Nakano, Haojie Yu, Shunsuke Katsuki, Minjin Lee, Meissner Torsten, Max Friesen, Lance S. Davidow, Leon Ptaszek, Takaaki Abe, Lee L. Rubin, Alexandre C. Pereira, Masanori Aikawa, Chad A. Cowan

Issue&Volume: 2020-05-14

Abstract: Although susceptibility to cardiovascular disease (CVD) is different for every patient,why some patients with type 2 diabetes mellitus (T2DM) develop CVD while others areprotected has not yet been clarified. Using T2DM-patient-derived human induced pluripotentstem cells (hiPSCs), we found that in patients protected from CVD, there was significantlyelevated expression of an esterase, arylacetamide deacetylase (AADAC), in vascularsmooth muscle cells (VSMCs). We overexpressed this esterase in human primary VSMCsand VSMCs differentiated from hiPSCs and observed that the number of lipid dropletswas significantly diminished. Further metabolomic analyses revealed a marked reductionin storage lipids and an increase in membrane phospholipids, suggesting changes inthe Kennedy pathway of lipid bioassembly. Cell migration and proliferation were alsosignificantly decreased in AADAC-overexpressing VSMCs. Moreover, apolipoprotein E(Apoe)-knockout mice overexpressing VSMC-specific Aadac showed amelioration of atheroscleroticlesions. Our findings suggest that higher AADAC expression in VSMCs protects T2DMpatients from CVD.

DOI: 10.1016/j.stem.2020.04.018

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30157-0

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