How vascular smooth muscle cell phenotype switching contributes to vascular disease

Cell Commun Signal. 2022 Nov 21;20(1):180. doi: 10.1186/s12964-022-00993-2.

Abstract

Vascular smooth muscle cells (VSMCs) are the most abundant cell in vessels. Earlier experiments have found that VSMCs possess high plasticity. Vascular injury stimulates VSMCs to switch into a dedifferentiated type, also known as synthetic VSMCs, with a high migration and proliferation capacity for repairing vascular injury. In recent years, largely owing to rapid technological advances in single-cell sequencing and cell-lineage tracing techniques, multiple VSMCs phenotypes have been uncovered in vascular aging, atherosclerosis (AS), aortic aneurysm (AA), etc. These VSMCs all down-regulate contractile proteins such as α-SMA and calponin1, and obtain specific markers and similar cellular functions of osteoblast, fibroblast, macrophage, and mesenchymal cells. This highly plastic phenotype transformation is regulated by a complex network consisting of circulating plasma substances, transcription factors, growth factors, inflammatory factors, non-coding RNAs, integrin family, and Notch pathway. This review focuses on phenotypic characteristics, molecular profile and the functional role of VSMCs phenotype landscape; the molecular mechanism regulating VSMCs phenotype switching; and the contribution of VSMCs phenotype switching to vascular aging, AS, and AA. Video Abstract.

Keywords: Aortic aneurysm; Atherosclerosis; Phenotype switching; Vascular aging; Vascular smooth muscle cells.

Publication types

  • Video-Audio Media
  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Atherosclerosis* / metabolism
  • Cell Proliferation
  • Humans
  • Muscle, Smooth, Vascular / physiology
  • Phenotype
  • Vascular System Injuries* / metabolism