Skip to Content
Merck
  • Myostatin Inhibits Vascular Smooth Muscle Cell Proliferation and Local 14q32 microRNA Expression, But Not Systemic Inflammation or Restenosis.

Myostatin Inhibits Vascular Smooth Muscle Cell Proliferation and Local 14q32 microRNA Expression, But Not Systemic Inflammation or Restenosis.

International journal of molecular sciences (2020-05-21)
Eveline A C Goossens, Margreet R de Vries, J Wouter Jukema, Paul H A Quax, A Yaël Nossent
ABSTRACT

Myostatin is a negative regulator of muscle cell growth and proliferation. Furthermore, myostatin directly affects the expression of 14q32 microRNAs by binding the 14q32 locus. Direct inhibition of 14q32 microRNA miR-495-3p decreased postinterventional restenosis via inhibition of both vascular smooth muscle cell (VSMC) proliferation and local inflammation. Here, we aimed to investigate the effects of myostatin in a mouse model for postinterventional restenosis. In VSMCs in vitro, myostatin led to the dose-specific downregulation of 14q32 microRNAs miR-433-3p, miR-494-3p, and miR-495-3p. VSMC proliferation was inhibited, where cell migration and viability remained unaffected. In a murine postinterventional restenosis model, myostatin infusion did not decrease restenosis, neointimal area, or lumen stenosis. Myostatin inhibited expression of both proliferation marker PCNA and of 14q32 microRNAs miR-433-3p, miR-494-3p, and miR-495-3p dose-specifically in cuffed femoral arteries. However, 14q32 microRNA expression remained unaffected in macrophages and macrophage activation as well as macrophage influx into lesions were not decreased. In conclusion, myostatin did not affect postinterventional restenosis. Although myostatin inhibits 14q32 microRNA expression and proliferation in VSMCs, myostatin had no effect on macrophage activation and infiltration. Our findings underline that restenosis is driven by both VSMC proliferation and local inflammation. Targeting only one of these components is insufficient to prevent restenosis.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Solketal methacrylate, 50 wt. % in dichloromethane, contains ~280 ppm 4-tert-butylcatechol as inhibitor
Sigma-Aldrich
Fetal Bovine Serum, non-USA origin, sterile-filtered, suitable for cell culture
Sigma-Aldrich
Hoechst 34580, Trihydrochloride salt, ≥98.0% (HPLC)