| Literature DB >> 32243809 |
Pei-Yu Chen1, Lingfeng Qin2, Guangxin Li3, Jose Malagon-Lopez4, Zheng Wang5, Sonia Bergaya6, Sharvari Gujja4, Alexander W Caulk7, Sae-Il Murtada7, Xinbo Zhang8, Zhen W Zhuang1, Deepak A Rao9, Guilin Wang10, Zuzana Tobiasova11, Bo Jiang12, Ruth R Montgomery13, Lele Sun14, Hongye Sun14, Edward A Fisher6, Jeffrey R Gulcher15, Carlos Fernandez-Hernando8, Jay D Humphrey7, George Tellides16, Thomas W Chittenden17, Michael Simons18.
Abstract
The etiology of aortic aneurysms is poorly understood, but it is associated with atherosclerosis, hypercholesterolemia, and abnormal transforming growth factor β (TGF-β) signaling in smooth muscle. Here, we investigated the interactions between these different factors in aortic aneurysm development and identified a key role for smooth muscle cell (SMC) reprogramming into a mesenchymal stem cell (MSC)-like state. SMC-specific ablation of TGF-β 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.Entities:
Keywords: TGF-beta; aneurysm; aorta; artificial intelligence; atherosclerosis; cell fate; cell reprogramming; mesenchymal stem cell; scRNA-seq; smooth muscle cells
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Year: 2020 PMID： 32243809 PMCID： PMC7182079 DOI： 10.1016/j.stem.2020.02.013
Source DB: PubMed Journal: Cell Stem Cell ISSN： 1875-9777 Impact factor: 24.633