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.

中文翻译：

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主动脉瘤中的平滑肌细胞重编程。

主动脉瘤的病因尚不清楚，但它与动脉粥样硬化、高胆固醇血症和平滑肌中异常转化生长因子 β (TGF-β) 信号传导有关。在这里，我们研究了主动脉瘤发展中这些不同因素之间的相互作用，并确定了平滑肌细胞（SMC）重编程为间充质干细胞（MSC）样状态的关键作用。在高胆固醇饮食的 Apoe-/- 小鼠中，SMC 特异性消融 TGF-β 信号导致主动脉瘤的发展，表现出人类疾病的所有特征，这与收缩性 SMC 子集转分化为 MSC 样中间体有关产生成骨细胞、软骨细胞、脂肪细胞和巨噬细胞的状态。内侧 SMC 损失与非 SMC 主动脉细胞量显着增加的结合诱导了主动脉的旺盛生长和扩张、主动脉壁的钙化和骨化以及炎症，导致动脉瘤的发展。