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The Ryanodine Receptor Contributes to the Lysophosphatidylcholine-Induced Mineralization in Valvular Interstitial Cells.
Wilson, Reid L; Sylvester, Christopher B; Wiltz, Dena C; Kumar, Aditya; Malik, Tahir H; Morrisett, Joel D; Grande-Allen, K Jane.
Afiliación
  • Wilson RL; Department of Bioengineering, Rice University, 6100 Main St., MS 142, Houston, TX, 77005, USA.
  • Sylvester CB; Medical Scientist Training Program, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.
  • Wiltz DC; Department of Bioengineering, Rice University, 6100 Main St., MS 142, Houston, TX, 77005, USA.
  • Kumar A; Medical Scientist Training Program, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.
  • Malik TH; Department of Bioengineering, Rice University, 6100 Main St., MS 142, Houston, TX, 77005, USA.
  • Morrisett JD; Department of Bioengineering, Rice University, 6100 Main St., MS 142, Houston, TX, 77005, USA.
  • Grande-Allen KJ; Department of Bioengineering, Rice University, 6100 Main St., MS 142, Houston, TX, 77005, USA.
Cardiovasc Eng Technol ; 11(3): 316-327, 2020 06.
Article en En | MEDLINE | ID: mdl-32356274
PURPOSE: Fibrocalcific aortic valve disease (CAVD) is caused by the deposition of calcific nodules in the aortic valve leaflets, resulting in progressive loss of function that ultimately requires surgical intervention. This process is actively mediated by the resident valvular interstitial cells (VICs), which, in response to oxidized lipids, transition from a quiescent to an osteoblast-like state. The purpose of this study was to examine if the ryanodine receptor, an intracellular calcium channel, could be therapeutically targeted to prevent this phenotypic conversion. METHODS: The expression of the ryanodine receptor in porcine aortic VICs was characterized by qRT-PCR and immunofluorescence. Next, the VICs were exposed to lysophosphatidylcholine, an oxidized lipid commonly found in low-density lipoprotein, while the activity of the ryanodine receptor was modulated with ryanodine. The cultures were analyzed for markers of cellular mineralization, alkaline phosphatase activity, proliferation, and apoptosis. RESULTS: Porcine aortic VICs predominantly express isoform 3 of the ryanodine receptors, and this protein mediates the cellular response to LPC. Exposure to LPC caused elevated intracellular calcium concentration in VICs, raised levels of alkaline phosphatase activity, and increased calcific nodule formation, but these changes were reversed when the activity of the ryanodine receptor was blocked. CONCLUSIONS: Our findings suggest blocking the activity of the ryanodine receptor can attenuate the valvular mineralization caused by LPC. We conclude that oxidized lipids, such as LPC, play an important role in the development and progression of CAVD and that the ryanodine receptor is a promising target for pharmacological intervention.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Válvula Aórtica / Calcinosis / Agonistas de los Canales de Calcio / Lisofosfatidilcolinas / Calcio / Canal Liberador de Calcio Receptor de Rianodina Límite: Animals Idioma: En Revista: Cardiovasc Eng Technol Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Válvula Aórtica / Calcinosis / Agonistas de los Canales de Calcio / Lisofosfatidilcolinas / Calcio / Canal Liberador de Calcio Receptor de Rianodina Límite: Animals Idioma: En Revista: Cardiovasc Eng Technol Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos