Cell stem cell · 2020
Smooth Muscle Cell Reprogramming in Aortic Aneurysms.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Chen Pei-Yu, Qin Lingfeng, Li Guangxin, Malagon-Lopez Jose, Wang Zheng, Bergaya Sonia, Gujja Sharvari, Caulk Alexander W, Murtada Sae-Il, Zhang Xinbo, Zhuang Zhen W, Rao Deepak A, Wang Guilin, Tobiasova Zuzana, Jiang Bo, Montgomery Ruth R, Sun Lele, Sun Hongye, Fisher Edward A, Gulcher Jeffrey R, Fernandez-Hernando Carlos, Humphrey Jay D, Tellides George, Chittenden Thomas W, Simons Michael
Аннотация
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.