Smooth muscle cell-driven vascular diseases and molecular mechanisms of VSMC plasticity

Cell Signal. 2018 Dec;52:48-64. doi: 10.1016/j.cellsig.2018.08.019. Epub 2018 Aug 30.

Abstract

Vascular smooth muscle cells (VSMCs) are the major cell type in blood vessels. Unlike many other mature cell types in the adult body, VSMC do not terminally differentiate but retain a remarkable plasticity. Fully differentiated medial VSMCs of mature vessels maintain quiescence and express a range of genes and proteins important for contraction/dilation, which allows them to control systemic and local pressure through the regulation of vascular tone. In response to vascular injury or alterations in local environmental cues, differentiated/contractile VSMCs are capable of switching to a dedifferentiated phenotype characterized by increased proliferation, migration and extracellular matrix synthesis in concert with decreased expression of contractile markers. Imbalanced VSMC plasticity results in maladaptive phenotype alterations that ultimately lead to progression of a variety of VSMC-driven vascular diseases. The nature, extent and consequences of dysregulated VSMC phenotype alterations are diverse, reflecting the numerous environmental cues (e.g. biochemical factors, extracellular matrix components, physical) that prompt VSMC phenotype switching. In spite of decades of efforts to understand cues and processes that normally control VSMC differentiation and their disruption in VSMC-driven disease states, the crucial molecular mechanisms and signalling pathways that shape the VSMC phenotype programme have still not yet been precisely elucidated. In this article we introduce the physiological functions of vascular smooth muscle/VSMCs, outline VSMC-driven cardiovascular diseases and the concept of VSMC phenotype switching, and review molecular mechanisms that play crucial roles in the regulation of VSMC phenotypic plasticity.

Keywords: Phenotype switching; Signalling pathways; Vascular smooth muscle; Vascular smooth muscle cell; Vasoproliferative disease.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Plasticity*
  • Cell Proliferation
  • Cells, Cultured
  • Epigenesis, Genetic
  • Extracellular Matrix / metabolism
  • Humans
  • Muscle, Smooth, Vascular / pathology*
  • Myocytes, Smooth Muscle / metabolism
  • Myocytes, Smooth Muscle / pathology*
  • Phenotype
  • Signal Transduction
  • Vascular Diseases / genetics*
  • Vascular Diseases / metabolism*
  • Vascular Diseases / pathology*