Distinct patterns of responses in endothelial cells and smooth muscle cells following vascular injury

JCI Insight. 2022 Oct 24;7(20):e153769. doi: 10.1172/jci.insight.153769.

Abstract

Vascular smooth muscle cells (SMCs) are heterogeneous, and their differential responses to vascular injury are not well understood. To address this question, we performed single-cell analysis of vascular cells to a ligation injury in mouse carotid arteries after 3 days. While endothelial cells had a homogeneous activation of mesenchymal genes, less than 30% of SMCs responded to the injury and generated 2 distinct clusters - i.e., proinflammatory SMCs and stress-responsive SMCs. Proinflammatory SMCs were enriched with high levels of inflammatory markers such as vascular cell adhesion molecule-1 while stress-responsive SMCs overexpressed heat shock proteins. Trajectory analysis suggested that proinflammatory SMCs were potentially derived from a specific subpopulation of SMCs. Ligand-receptor pair analysis showed that the interaction between macrophages and proinflammatory SMCs was the major cell-cell communication among all cell types in the injured arteries. In vitro coculture demonstrated that VCAM1+ SMCs had a stronger chemotactic effect on macrophage recruitment than VCAM1- SMCs. Consistently, the number of VCAM1+ SMCs significantly increased in injured arteries and atherosclerotic lesions of ApoE-/- mice and human arteries. These findings provide insights at the single-cell level on the distinct patterns of endothelial cells and SMC responses to vascular injury.

Keywords: Cardiovascular disease; Vascular Biology.

Publication types

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

MeSH terms

  • Animals
  • Apolipoproteins E / genetics
  • Apolipoproteins E / metabolism
  • Endothelial Cells* / metabolism
  • Heat-Shock Proteins / metabolism
  • Humans
  • Ligands
  • Mice
  • Mice, Knockout, ApoE
  • Muscle, Smooth, Vascular
  • Myocytes, Smooth Muscle / metabolism
  • Vascular Cell Adhesion Molecule-1 / metabolism
  • Vascular System Injuries* / metabolism

Substances

  • Vascular Cell Adhesion Molecule-1
  • Ligands
  • Apolipoproteins E
  • Heat-Shock Proteins