Emerging role of YAP/TAZ in vascular mechanotransduction and disease

Microcirculation. 2024 May;31(4):e12838. doi: 10.1111/micc.12838. Epub 2023 Nov 27.

Abstract

Cells have an incredible ability to physically interact with neighboring cells and their environment. They can detect and respond to mechanical forces by converting mechanical stimuli into biochemical signals in a process known as mechanotransduction. This is a key process for the adaption of vascular smooth muscle and endothelial cells to altered flow and pressure conditions. Mechanical stimuli, referring to a physical force exerted on cells, are primarily sensed by transmembrane proteins and the actin cytoskeleton, which initiate a cascade of intracellular events, including the activation of signaling pathways, ion channels, and transcriptional regulators. Recent work has highlighted an important role of the transcriptional coactivators YAP/TAZ for mechanotransduction in vascular cells. Interestingly, the activity of YAP/TAZ decreases with age, providing a potential mechanism for the detrimental effects of aging in the vascular wall. In this review, we summarize the current knowledge on the functional role of YAP and TAZ in vascular endothelial and smooth muscle cells for mechanotransduction in homeostasis and disease. In particular, the review is focused on in vivo observations from conditional knockout (KO) models of YAP/TAZ and the potential implications these studies may have for our understanding of vascular disease development.

Keywords: WWTR1; YAP1; atherosclerosis; endothelial cells; smooth muscle cells.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing* / metabolism
  • Animals
  • Cell Cycle Proteins / metabolism
  • Endothelial Cells / metabolism
  • Humans
  • Mechanotransduction, Cellular* / physiology
  • Muscle, Smooth, Vascular / metabolism
  • Trans-Activators / metabolism
  • Transcription Factors* / metabolism
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins / metabolism
  • Vascular Diseases / metabolism
  • Vascular Diseases / physiopathology
  • YAP-Signaling Proteins* / metabolism

Substances

  • Transcription Factors
  • YAP-Signaling Proteins
  • Adaptor Proteins, Signal Transducing
  • YAP1 protein, human
  • Trans-Activators
  • Cell Cycle Proteins
  • WWTR1 protein, human
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins