Smooth Muscle Cell Reprogramming in Aortic Aneurysms

Cell Stem Cell. 2020 Apr 2;26(4):542-557.e11. doi: 10.1016/j.stem.2020.02.013.


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.

Keywords: TGF-beta; aneurysm; aorta; artificial intelligence; atherosclerosis; cell fate; cell reprogramming; mesenchymal stem cell; scRNA-seq; smooth muscle cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta
  • Aortic Aneurysm*
  • Cellular Reprogramming
  • Mice
  • Muscle, Smooth, Vascular*
  • Myocytes, Smooth Muscle
  • Transforming Growth Factor beta


  • Transforming Growth Factor beta