Nanotechnology Enabled Modulation of Signaling Pathways Affects Physiologic Responses in Intact Vascular Tissue

Tissue Eng Part A. 2019 Mar;25(5-6):416-426. doi: 10.1089/ten.TEA.2018.0169. Epub 2018 Oct 26.

Abstract

Subarachnoid hemorrhage (SAH) is associated with vasospasm that is refractory to traditional vasodilators, and inhibition of vasospasm after SAH remains a large unmet clinical need. SAH causes changes in the phosphorylation state of the small heat shock proteins (HSPs), HSP20 and HSP27, in the vasospastic vessels. In this study, the levels of HSP27 and HSP20 were manipulated using nanotechnology to mimic the intracellular phenotype of SAH-induced vasospasm, and the effect of this manipulation was tested on vasomotor responses in intact tissues. This work provides insight into potential therapeutic targets for the development of more effective treatments for SAH induced vasospasm.

Keywords: HSP20; HSP27; endosomolytic polymer; nanotechnology; smooth muscle contraction; subarachnoid hemorrhage.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Actins / metabolism
  • Animals
  • Blood Vessels / physiology*
  • Calcium / metabolism
  • Gene Silencing
  • Heat-Shock Proteins / metabolism
  • Humans
  • Micelles
  • Muscle Contraction
  • Muscle, Smooth / physiology
  • Nanoparticles / chemistry
  • Nanotechnology / methods*
  • Peptides / chemistry
  • Peptides / metabolism
  • Polymerization
  • RNA, Small Interfering / metabolism
  • Rats
  • Signal Transduction*
  • Static Electricity

Substances

  • Actins
  • Heat-Shock Proteins
  • Micelles
  • Peptides
  • RNA, Small Interfering
  • Calcium