Smooth Muscle Cell Reprogramming in Aortic Aneurysms

被引：161

作者：

Chen, Pei-Yu ^{[1
]}

Qin, Lingfeng ^{[2
]}

Li, Guangxin ^{[2
,3
]}

Malagon-Lopez, Jose ^{[4
,5
]}

Wang, Zheng ^{[6
]}

Bergaya, Sonia ^{[7
,8
]}

Gujja, Sharvari ^{[4
,5
]}

Caulk, Alexander W. ^{[9
]}

Murtada, Sae-Il ^{[9
]}

Zhang, Xinbo ^{[10
,11
,12
]}

Zhuang, Zhen W. ^{[1
]}

Rao, Deepak A. ^{[13
,14
]}

Wang, Guilin ^{[15
]}

Tobiasova, Zuzana ^{[16
]}

Jiang, Bo ^{[2
,17
]}

Montgomery, Ruth R. ^{[18
]}

Sun, Lele ^{[19
]}

Sun, Hongye ^{[19
]}

Fisher, Edward A. ^{[7
,8
]}

Gulcher, Jeffrey R. ^{[20
]}

Fernandez-Hernando, Carlos ^{[10
,11
,12
]}

Humphrey, Jay D. ^{[9
]}

Tellides, George ^{[2
]}

Chittenden, Thomas W. ^{[4
,5
,21
]}

Simons, Michael ^{[1
,22
]}

机构：

[1] Yale Univ, Sch Med, Dept Internal Med, Yale Cardiovasc Res Ctr, New Haven, CT 06510 USA

[2] Yale Univ, Sch Med, Dept Surg, New Haven, CT 06510 USA

[3] Peking Univ, Dept Breast & Thyroid Surg, Shenzhen Hosp, 1120 Lianhua Rd, Shenzhen, Guangdong, Peoples R China

[4] WuXiNextCODE, Adv Artificial Intelligence Res Lab, Computat Stat & Bioinformat Grp, Cambridge, MA 02142 USA

[5] Complex Biol Syst Alliance, Medford, MA 02155 USA

[6] Qingdao Univ, Sch Basic Med, Qingdao, Shandong, Peoples R China

[7] NYU, Marc & Ruti Bell Program Vasc Biol, Dept Med Cardiol, Sch Med, New York, NY USA

[8] NYU, Ctr Prevent Cardiovasc Dis, Sch Med, New York, NY USA

[9] Yale Univ, Dept Biomed Engn, New Haven, CT USA

[10] Yale Univ, Vasc Biol & Therapeut Program, Sch Med, New Haven, CT USA

[11] Yale Univ, Dept Comparat Med, Sch Med, Integrat Cell Signaling & Neurobiol Metab Program, New Haven, CT USA

[12] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA

[13] Brigham & Womens Hosp, Div Rheumatol Inflammat Immun, 75 Francis St, Boston, MA 02115 USA

[14] Harvard Med Sch, Boston, MA 02115 USA

[15] Yale Univ, Sch Med, Dept Mol Biophys & Biochem, New Haven, CT 06510 USA

[16] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT USA

[17] China Med Univ, Dept Vasc Surg, Hosp 1, Shenyang, Peoples R China

[18] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA

[19] WuXiNextCODE, Genom Lab, Shanghai, Peoples R China

[20] WuXi NextCODE, Canc Genet Grp, Cambridge, MA USA

[21] Harvard Med Sch, Boston Childrens Hosp, Div Genet & Genom, Boston, MA 02115 USA

[22] Yale Univ, Sch Med, Dept Cell Biol, New Haven, CT 06510 USA

来源：

CELL STEM CELL | 2020年 / 26卷 / 04期

关键词：

GROWTH; ATHEROSCLEROSIS; RECEPTOR;

D O I：

10.1016/j.stem.2020.02.013

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

The etiology of aortic aneurysms is poorly understood, but it is associated with atherosclerosis, hypercholesterolemia, and abnormal transforming growth factor beta (TGF-beta) signaling in smooth muscle. Here, we investigated the interactions between these different factors in aortic aneurysmdevelopment and identified a key role for smooth muscle cell (SMC) reprogramming into a mesenchymal stem cell (MSC)like state. SMC-specific ablation of TGF-beta signaling in Apoe(-/-) mice on a hypercholesterolemic diet led to development of aortic aneurysms exhibiting all the features of human disease, which was associated with transdifferentiation of a subset of contractile SMCs into an MSC-like intermediate state that generated osteoblasts, chondrocytes, adipocytes, and macrophages. This combination of medial SMC loss with marked increases in non-SMC aortic cell mass induced exuberant growth and dilation of the aorta, calcification and ossification of the aortic wall, and inflammation, resulting in aneurysm development.

引用

页码：542 / +

页数：27

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