Yes-associated protein reacts differently in vascular smooth muscle cells under different intensities of mechanical stretch

Aging (Albany NY). 2022 Jan 4;14(1):286-296. doi: 10.18632/aging.203768. Epub 2022 Jan 4.

Abstract

Vascular smooth muscle cells (VSMCs) are stromal cells of the vascular wall and are continually exposed to mechanical signals. The loss of VSMCs is closely related to the occurrence of many vascular diseases, such as aortic aneurysms and aortic dissection. The proliferation and apoptosis of VSMCs are mechanically stimulated. Yes-associated protein (YAP), one of the core components of the Hippo pathway, plays a key role in the response of VSMCs to mechanical signals. In this study, we tested the impact of different intensities of mechanical stretch on the proliferation and apoptosis of VSMCs, as well as YAP. We tested VSMCs' proliferation and apoptosis and YAP reaction via immunocytochemistry, western blotting, CCK-8 and flow cytometric analysis. We found that 10% elongation could increase the phosphorylation of YAP and prevent it from entering the nucleus, as well as inhibit cell proliferation and promote apoptosis. However, 15% elongation reduced YAP phosphorylation and promoted its nuclear entry, thereby promoting cell proliferation and inhibiting apoptosis. Accordingly, YAP knockdown suppressed the phenotype of VMSCs induced by 15% elongation. Taken together, YAP regulates proliferation and apoptosis of VSMCs differently under different intensity of mechanical stretch. Mechanical stretch with appropriate intensity can promote the proliferation and inhibit apoptosis of VSMCs by activating YAP.

Keywords: Hippo pathway; YAP; apoptosis; mechanical stretch; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / pharmacology
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Cell Proliferation / drug effects
  • Cell Proliferation / physiology
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation / drug effects
  • Hippo Signaling Pathway / physiology
  • Male
  • Mechanotransduction, Cellular / physiology
  • Muscle, Smooth, Vascular / physiology*
  • Myocytes, Smooth Muscle / physiology*
  • Pyridines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Rho Factor / genetics
  • Rho Factor / metabolism
  • Stress, Mechanical*
  • Vasodilation / physiology*
  • YAP-Signaling Proteins / genetics
  • YAP-Signaling Proteins / metabolism*
  • rho-Associated Kinases / genetics
  • rho-Associated Kinases / metabolism

Substances

  • Amides
  • Enzyme Inhibitors
  • Pyridines
  • Rho Factor
  • YAP-Signaling Proteins
  • Yap1 protein, rat
  • Y 27632
  • rho-Associated Kinases