Adventitial MSC-like Cells Are Progenitors of Vascular Smooth Muscle Cells and Drive Vascular Calcification in Chronic Kidney Disease.
Adventitial MSC-like Cells Are Progenitors of Vascular Smooth Muscle Cells and Drive Vascular Calcification in Chronic Kidney Disease.
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DOI：
10.1016/j.stem.2016.08.001
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发表时间：
2016-11-03
期刊：
影响因子：
23.9
通讯作者：
Humphreys, Benjamin D.
中科院分区：
文献类型：
--
作者：
Kramann, Rafael;Goettsch, Claudia;Wongboonsin, Janewit;Iwata, Hiroshi;Schneider, Rebekka K.;Kuppe, Christoph;Kaesler, Nadine;Chang-Panesso, Monica;Machado, Flavia G.;Gratwohl, Susannah;Madhurima, Kaushal;Hutcheson, Joshua D.;Jain, Sanjay;Aikawa, Elena;Humphreys, Benjamin D.
间充质干细胞样细胞(MSC样细胞)存在于血管壁，但其在血管再生和疾病中的作用尚不清楚。在这里，我们发现位于动脉外膜的Gli1+细胞是血管平滑肌细胞的前体细胞，并有助于股动脉急性损伤后新生内膜的形成和修复。遗传命运追踪表明，在患有慢性肾脏疾病的载脂蛋白E−/−小鼠的动脉粥样硬化和动脉硬化过程中，外膜Gli1+间充质干细胞样细胞迁移到中膜和新生内膜。我们的数据表明，在中膜和内膜钙化过程中，Gli1+细胞是成骨细胞样细胞的主要来源。在诱导肾脏损伤之前对Gli1+细胞进行基因消融，显著降低了血管钙化的严重程度。这些发现表明，Gli1+细胞在急性和慢性损伤后的血管重塑中是关键的外膜前体细胞，并提示它们可能是缓解血管钙化的相关治疗靶点。ETOC：Kramann等人发现，存在于血管壁上的Gli1+MSC样细胞在损伤后分化为成骨样细胞，并对钙化做出了主要贡献。在损伤前切除这些细胞可以消除钙化，因此表明它们可能是治疗干预的目标。
Mesenchymal stem cell-like (MSC-like) cells reside in the vascular wall but their role in vascular regeneration and disease is poorly understood. Here, we show that Gli1+ cells located in the arterial adventitia are progenitors of vascular smooth muscle cells, and contribute to neointima formation and repair after acute injury to the femoral artery. Genetic fate tracing indicates that adventitial Gli1+ MSC-like cells migrate into the media and neointima during athero- and arteriosclerosis in ApoE−/− mice with chronic kidney disease. Our data indicate that Gli1+ cells are a major source of osteoblast-like cells during calcification in the media and intima. Genetic ablation of Gli1+ cells before induction of kidney injury dramatically reduced the severity of vascular calcification. These findings implicate Gli1+ cells as critical adventitial progenitors in vascular remodeling after acute and during chronic injury and suggest that they may be relevant therapeutic targets for mitigation of vascular calcification. eTOC: Kramann et al show that Gli1+ MSC-like cells that reside in the vascular wall differentiate into osteoblast like cells after injury and make a major contribution to calcification. Ablation of these cells before injury eliminates calcification, and therefore suggests that they could be a target for therapeutic intervention.
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DOI：
10.1161/atvbaha.110.209692
发表时间：
2010-10-01
影响因子：
8.7
作者：
Daniel, Jan-Marcus;Bielenberg, Wiebke;Sedding, Daniel G.
通讯作者：
Sedding, Daniel G.
DOI：
10.1161/atvbaha.111.223701
发表时间：
2011-06
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Nemenoff RA;Horita H;Ostriker AC;Furgeson SB;Simpson PA;VanPutten V;Crossno J;Offermanns S;Weiser-Evans MC
通讯作者：
Weiser-Evans MC
影响因子：
15.3
作者：
Bunting, C H
通讯作者：
Bunting, C H
影响因子：
37.8
作者：
Bentzon, Jacob F.;Sondergaard, Claus S.;Falk, Erling
通讯作者：
Falk, Erling
影响因子：
4.4
作者：
Hutcheson JD;Maldonado N;Aikawa E
通讯作者：
Aikawa E