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Platelet-derived microvesicles regulate vascular smooth muscle cell energy metabolism via PRKAA after intimal injury

Jing Yan1, Yang-Jing Fan1, Han Bao1

  • 1Institute of Mechanobiology & Medical Engineering, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.

Journal of Cell Science
|March 17, 2022
PubMed

Insights

Collagen-activated platelet-derived microvesicles (aPMVs) alter vascular smooth muscle cell (VSMC) metabolism, promoting hyperplasia. Inhibiting the Pka-PRKAA-FoxO1 pathway with Compound C reversed these effects, offering a therapeutic target.

Area of Science:

  • Cardiovascular Biology
  • Cellular Metabolism
  • Vascular Biology

Background:

  • Vascular intimal injury triggers cardiovascular diseases.
  • Platelet activation and microvesicle secretion occur upon collagen exposure.
  • Vascular smooth muscle cells (VSMCs) exhibit abnormal metabolism and proliferation when exposed to microvesicles, contributing to neointimal hyperplasia.

Purpose of the Study:

  • To investigate the role of collagen-activated platelet-derived microvesicles (aPMVs) in VSMC energy metabolism.
  • To elucidate the signaling pathway through which aPMVs affect VSMC function.
  • To evaluate the therapeutic potential of targeting this pathway for neointimal hyperplasia.

Main Methods:

  • Carotid artery intimal injury model in vivo.
  • In vitro studies using VSMCs exposed to aPMVs.
  • Analysis of protein phosphorylation (Pka, PRKAA, FoxO1) and cellular metabolism (glycolysis, oxidative phosphorylation).
  • Assessment of VSMC migration, proliferation, and neointimal formation.
  • Pharmacological inhibition of PRKAA using Compound C.

Main Results:

  • aPMVs increased phosphorylated Pka content.
  • aPMVs reduced VSMC glycolysis and increased oxidative phosphorylation.
  • aPMVs promoted VSMC migration and proliferation via upregulated phosphorylated PRKAA and FoxO1.
  • Compound C reversed aPMV-induced changes in VSMC function and energy metabolism, and inhibited neointimal formation.

Conclusions:

  • aPMVs modulate VSMC energy metabolism through the Pka-PRKAA-FoxO1 pathway.
  • This metabolic shift promotes VSMC proliferation and migration, contributing to neointimal hyperplasia.
  • Targeting the aPMV-induced metabolic reprogramming of VSMCs presents a potential therapeutic strategy for preventing vascular hyperplasia.
Keywords:
Cell energy metabolismIntimal injuryPRKAAPlatelet-derived microvesiclesVascular smooth muscle cells

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