Over-expression of Neuron-derived Orphan Receptor-1 (NOR-1) exacerbates neointimal hyperplasia after vascular injury - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Human Molecular Genetics Année : 2013

Over-expression of Neuron-derived Orphan Receptor-1 (NOR-1) exacerbates neointimal hyperplasia after vascular injury

Ricardo Rodríguez-Calvo
  • Fonction : Auteur
Anna Guadall
  • Fonction : Auteur
María A Navarro
  • Fonction : Auteur
Judith Alonso
  • Fonction : Auteur
Beatriz Ferrán
  • Fonction : Auteur
Alicia de Diego
  • Fonction : Auteur
Pedro Muniesa
  • Fonction : Auteur
Jesus Osada
  • Fonction : Auteur
Cristina Rodríguez
  • Fonction : Auteur
José Martinez-Gonzalez
  • Fonction : Auteur

Résumé

We have previously shown that NOR-1 (NR4A3) modulates the proliferation and survival of vascular cells in culture. However, in genetically modified animal models, somewhat conflicting results have been reported concerning the involvement of NOR-1 in neointimal formation after vascular injury. The aim of this study was to generate a transgenic mouse model over-expressing NOR-1 in smooth muscle cells (SMCs) and assess the consequence of a gain of function of this receptor on intimal hyperplasia after vascular injury. The transgene construct (SM22-NOR1) was prepared by ligating the full-length human NOR-1 cDNA (hNOR-1) and a mouse SM22a minimal promoter able to drive NOR-1 expression to SMC. Two founders were generated and two stable transgenic mouse lines (TgNOR-1) were established by backcrossing the transgene-carrying founders with C57BL/6J mice. Real-time PCR and immunohistochemistry confirmed that hNOR-1 was mainly targeted to vascular beds such as aorta and carotid arteries, and was similar in both transgenic lines. Vascular SMC from transgenic animals exhibit increased NOR-1 transcriptional activity (assessed by electrophoretic mobility shift assay and luciferase assays), increased mitogenic activity (determined by [ 3 H]-thymidine incorporation; 1.58-fold induction, P < 0.001) and increased expression of embryonic smooth muscle myosin heavy chain (SMemb) than wild-type cells from control littermates. Using the carotid artery ligation model, we show that neointima formation was increased in transgenic versus wild-type mice (2.36-fold induction, P < 0.01). Our in vivo data support a role for NOR-1 in VSMC proliferation and vascular remodelling. This NOR-1 transgenic mouse could be a useful model to study fibroproliferative vascular diseases.
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Dates et versions

hal-03026064 , version 1 (26-11-2020)

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Ricardo Rodríguez-Calvo, Anna Guadall, Olivier Calvayrac, María A Navarro, Judith Alonso, et al.. Over-expression of Neuron-derived Orphan Receptor-1 (NOR-1) exacerbates neointimal hyperplasia after vascular injury. Human Molecular Genetics, 2013, 22 (10), pp.1949-1959. ⟨10.1093/hmg/ddt042⟩. ⟨hal-03026064⟩
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