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Inositol 1,4,5-Trisphosphate Receptors Regulate Vascular Smooth Muscle Cell Proliferation and Neointima Formation in

Fang Huang1, Fei Zhang1, Lei Huang1

  • 1Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School Peking University Shenzhen China.

Journal of the American Heart Association
|July 18, 2024
PubMed
Abstract

Insights

Inositol 1,4,5-trisphosphate receptors (IP3Rs) mediate calcium release crucial for vascular smooth muscle cell proliferation and arterial disease development. Targeting IP3Rs may offer new therapeutic strategies for neointima hyperplasia.

Area of Science:

  • Cardiovascular Biology
  • Cell Signaling
  • Molecular Medicine

Background:

  • Vascular smooth muscle cell (VSMC) proliferation contributes to arterial diseases like neointima hyperplasia.
  • Calcium ions (Ca2+) play a key role in VSMC proliferation.
  • The specific role of Ca2+ release via inositol 1,4,5-trisphosphate receptors (IP3Rs) in VSMC proliferation is not fully understood.

Purpose of the Study:

  • To investigate the role of IP3Rs in regulating VSMC proliferation and neointima formation.
  • To elucidate the signaling pathways involved in IP3R-mediated VSMC proliferation.

Main Methods:

  • Utilized in vitro cell culture and in vivo mouse models.
  • Examined IP3R subtype expression under stimulated conditions and in arterial injury models.
  • Generated genetic knockout models to assess the impact of IP3R ablation on VSMC proliferation, migration, and neointima formation.

Main Results:

  • IP3R expression increased in VSMCs upon stimulation and in injured arteries.
  • Genetic ablation of IP3Rs abolished ER Ca2+ release, reduced VSMC proliferation and migration, and attenuated neointima formation.
  • IP3R-mediated Ca2+ release activated cAMP response element-binding protein (CREB) via Ca2+/calmodulin-dependent protein kinase II and Akt, which was suppressed in IP3R-deficient cells.

Conclusions:

  • IP3R-mediated Ca2+ release is essential for regulating CREB activation, VSMC proliferation, and neointima formation.
  • This study highlights the critical role of IP3Rs in arterial disease pathogenesis.
  • IP3Rs represent a potential therapeutic target for preventing arterial restenosis.
Keywords:
Ca2+ signalingIP3 receptorcell proliferationneointima formationvascular remodelingvascular smooth muscle cell

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