Related Experiment Video
Updated: Aug 8, 2026
Murine Aortic Crush Injury: An Efficient In Vivo Model of Smooth Muscle Cell Proliferation and Endothelial Function
Published on: June 11, 2017
Sarco/endoplasmic reticulum Ca2+-ATPase gene transfer reduces vascular smooth muscle cell proliferation and neointima
Larissa Lipskaia1, Federica del Monte, Thierry Capiod
1INSERM U621/IFR-14, UPMC-CHU Pitié-Salpêtrière, Paris, France.
Abstract:
Proliferation of vascular smooth muscle cells (VSMC) is a primary cause of vascular disorders and is associated with major alterations in Ca2+ handling supported by loss of the sarco/endoplasmic reticulum calcium ATPase, SERCA2a. To determine the importance of SERCA2a in neointima formation, we have prevented loss of its expression by adenoviral gene transfer in a model of balloon injury of the rat carotid artery. Two weeks after injury, the intima/media ratio was significantly lower in SERCA2a-infected than in injured noninfected or injured beta-galactosidase-infected carotids (0.29+/-0.04 versus 0.89+/-0.19 and 0.72+/-0.14, respectively; P<0.05), and was comparable to that observed in control carotids (0.21+/-0.03). The pathways leading to proliferation were analyzed in serum-stimulated VSMC. Forced expression of SERCA2a arrested cell cycle at the G1 phase and prevented apoptosis. SERCA2a inhibits proliferation through inactivation of calcineurin (PP2B) and its target transcription factor NFAT (nuclear factor of activated T-cells) resulting in lowering of cyclin D1 and pRb levels. By using NFAT-competing peptide VIVIT, we showed that NFAT activity is strongly required to promote VSMC proliferation. In conclusion, we provide the first evidence that increasing SERCA2a activity inhibits VSMC proliferation and balloon injury-induced neointima formation.
Insights
Restoring sarco/endoplasmic reticulum calcium ATPase (SERCA2a) expression inhibits vascular smooth muscle cell proliferation and neointima formation after vascular injury. This study demonstrates SERCA2a
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Vascular Cell Biology
Background:
- Vascular smooth muscle cell (VSMC) proliferation drives vascular disorders.
- Loss of sarco/endoplasmic reticulum calcium ATPase (SERCA2a) impairs Ca2+ handling and promotes VSMC proliferation.
- Neointima formation following vascular injury is a critical pathological process.
Purpose of the Study:
- To investigate the role of SERCA2a in neointima formation after vascular injury.
- To determine if restoring SERCA2a expression can prevent or reduce neointima formation.
- To elucidate the molecular mechanisms by which SERCA2a influences VSMC proliferation.
Main Methods:
- Adenoviral gene transfer was used to restore SERCA2a expression in a rat carotid artery balloon injury model.
- Intima/media ratio was quantified 2 weeks post-injury.
- VSMC proliferation and apoptosis were analyzed in vitro, and cell cycle progression was assessed.
- The involvement of calcineurin (PP2B) and NFAT (nuclear factor of activated T-cells) signaling pathways was investigated.
Main Results:
- SERCA2a gene transfer significantly reduced the intima/media ratio compared to controls.
- Forced SERCA2a expression arrested VSMC cell cycle at G1 phase and prevented apoptosis.
- SERCA2a inhibited VSMC proliferation by inactivating calcineurin-NFAT signaling, leading to decreased cyclin D1 and pRb levels.
- NFAT activity was essential for VSMC proliferation, as demonstrated by VIVIT peptide experiments.
Conclusions:
- Increased SERCA2a activity effectively inhibits VSMC proliferation.
- Restoring SERCA2a expression reduces balloon injury-induced neointima formation.
- The findings highlight SERCA2a as a potential therapeutic target for vascular disorders.
