Vascular action of bisphosphonates: In vitro effect of alendronate on the regulation of cellular events involved in vessel pathogenesis
- Autores
- Cutini, Pablo Hernan; Rauschemberger, María Belén; Sandoval, Marisa Julia; Massheimer, Virginia Laura
- Año de publicación
- 2016
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- In this work we investigate whether, despite the procalcific action of alendronate on bone, the drug would be able to regulate in vitro the main cellular events that take part in atherosclerotic lesion generation. Using endothelial cell cultures we showed that Alendronate (1–50 μM) acutely enhances nitric oxide production (10–30 min). This stimulatory action of the bisphosphonate involves the participation of MAPK signaling transduction pathway. Under inflammatory stress, the drug reduces monocytes and platelets interactions with endothelial cells induced by lipopolysaccharide. Indeed the bisphophonate exhibits a significant inhibition of endothelial dependent platelet aggregation. The molecular mechanism of alendronate (ALN) on leukocyte adhesion depends on the regulation of the expression of cell adhesion related genes (VCAM-1; ICAM-1); meanwhile the antiplatelet activity is associated with the effect of the drug on nitric oxide production. On vascular smooth muscle cells, the drug exhibits ability to decrease osteogenic transdifferentiation and extracellular matrix mineralization. When vascular smooth muscle cells were cultured in osteogenic medium for 21 days, they exhibited an upregulation of calcification markers (RUNX2 and TNAP), high alkaline phosphatase activity and a great amount of mineralization nodules. ALN treatment significantly down-regulates mRNA levels of osteoblasts markers; diminishes alkaline phosphatase activity and reduces the extracellular calcium deposition. The effect of ALN on vascular cells differs from its own bone action. On calvarial osteoblasts ALN induces cell proliferation, enhances alkaline phosphatase activity, and increases mineralization, but does not affect nitric oxide synthesis. Our results support the hypothesis that ALN is an active drug at vascular level that regulates key processes involved in vascular pathogenesis through a direct action on vessel cells.
Fil: Cutini, Pablo Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina
Fil: Rauschemberger, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina
Fil: Sandoval, Marisa Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina
Fil: Massheimer, Virginia Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina - Materia
-
Alendronate
Endothelial Monocyte Adhesion
Nitric Oxide
Osteogenic Markers
Platelet Adhesion And Aggregation
Vascular Calcification - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/57353
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Vascular action of bisphosphonates: In vitro effect of alendronate on the regulation of cellular events involved in vessel pathogenesisCutini, Pablo HernanRauschemberger, María BelénSandoval, Marisa JuliaMassheimer, Virginia LauraAlendronateEndothelial Monocyte AdhesionNitric OxideOsteogenic MarkersPlatelet Adhesion And AggregationVascular Calcificationhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3In this work we investigate whether, despite the procalcific action of alendronate on bone, the drug would be able to regulate in vitro the main cellular events that take part in atherosclerotic lesion generation. Using endothelial cell cultures we showed that Alendronate (1–50 μM) acutely enhances nitric oxide production (10–30 min). This stimulatory action of the bisphosphonate involves the participation of MAPK signaling transduction pathway. Under inflammatory stress, the drug reduces monocytes and platelets interactions with endothelial cells induced by lipopolysaccharide. Indeed the bisphophonate exhibits a significant inhibition of endothelial dependent platelet aggregation. The molecular mechanism of alendronate (ALN) on leukocyte adhesion depends on the regulation of the expression of cell adhesion related genes (VCAM-1; ICAM-1); meanwhile the antiplatelet activity is associated with the effect of the drug on nitric oxide production. On vascular smooth muscle cells, the drug exhibits ability to decrease osteogenic transdifferentiation and extracellular matrix mineralization. When vascular smooth muscle cells were cultured in osteogenic medium for 21 days, they exhibited an upregulation of calcification markers (RUNX2 and TNAP), high alkaline phosphatase activity and a great amount of mineralization nodules. ALN treatment significantly down-regulates mRNA levels of osteoblasts markers; diminishes alkaline phosphatase activity and reduces the extracellular calcium deposition. The effect of ALN on vascular cells differs from its own bone action. On calvarial osteoblasts ALN induces cell proliferation, enhances alkaline phosphatase activity, and increases mineralization, but does not affect nitric oxide synthesis. Our results support the hypothesis that ALN is an active drug at vascular level that regulates key processes involved in vascular pathogenesis through a direct action on vessel cells.Fil: Cutini, Pablo Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaFil: Rauschemberger, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaFil: Sandoval, Marisa Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaFil: Massheimer, Virginia Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaAcademic Press Ltd - Elsevier Science Ltd2016-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/57353Cutini, Pablo Hernan; Rauschemberger, María Belén; Sandoval, Marisa Julia; Massheimer, Virginia Laura; Vascular action of bisphosphonates: In vitro effect of alendronate on the regulation of cellular events involved in vessel pathogenesis; Academic Press Ltd - Elsevier Science Ltd; Journal of Molecular and Cellular Cardiology; 100; 11-2016; 83-920022-2828CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0022282816303170info:eu-repo/semantics/altIdentifier/doi/10.1016/j.yjmcc.2016.08.017info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:48:56Zoai:ri.conicet.gov.ar:11336/57353instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:48:56.978CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Vascular action of bisphosphonates: In vitro effect of alendronate on the regulation of cellular events involved in vessel pathogenesis |
title |
Vascular action of bisphosphonates: In vitro effect of alendronate on the regulation of cellular events involved in vessel pathogenesis |
spellingShingle |
Vascular action of bisphosphonates: In vitro effect of alendronate on the regulation of cellular events involved in vessel pathogenesis Cutini, Pablo Hernan Alendronate Endothelial Monocyte Adhesion Nitric Oxide Osteogenic Markers Platelet Adhesion And Aggregation Vascular Calcification |
title_short |
Vascular action of bisphosphonates: In vitro effect of alendronate on the regulation of cellular events involved in vessel pathogenesis |
title_full |
Vascular action of bisphosphonates: In vitro effect of alendronate on the regulation of cellular events involved in vessel pathogenesis |
title_fullStr |
Vascular action of bisphosphonates: In vitro effect of alendronate on the regulation of cellular events involved in vessel pathogenesis |
title_full_unstemmed |
Vascular action of bisphosphonates: In vitro effect of alendronate on the regulation of cellular events involved in vessel pathogenesis |
title_sort |
Vascular action of bisphosphonates: In vitro effect of alendronate on the regulation of cellular events involved in vessel pathogenesis |
dc.creator.none.fl_str_mv |
Cutini, Pablo Hernan Rauschemberger, María Belén Sandoval, Marisa Julia Massheimer, Virginia Laura |
author |
Cutini, Pablo Hernan |
author_facet |
Cutini, Pablo Hernan Rauschemberger, María Belén Sandoval, Marisa Julia Massheimer, Virginia Laura |
author_role |
author |
author2 |
Rauschemberger, María Belén Sandoval, Marisa Julia Massheimer, Virginia Laura |
author2_role |
author author author |
dc.subject.none.fl_str_mv |
Alendronate Endothelial Monocyte Adhesion Nitric Oxide Osteogenic Markers Platelet Adhesion And Aggregation Vascular Calcification |
topic |
Alendronate Endothelial Monocyte Adhesion Nitric Oxide Osteogenic Markers Platelet Adhesion And Aggregation Vascular Calcification |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.2 https://purl.org/becyt/ford/3 |
dc.description.none.fl_txt_mv |
In this work we investigate whether, despite the procalcific action of alendronate on bone, the drug would be able to regulate in vitro the main cellular events that take part in atherosclerotic lesion generation. Using endothelial cell cultures we showed that Alendronate (1–50 μM) acutely enhances nitric oxide production (10–30 min). This stimulatory action of the bisphosphonate involves the participation of MAPK signaling transduction pathway. Under inflammatory stress, the drug reduces monocytes and platelets interactions with endothelial cells induced by lipopolysaccharide. Indeed the bisphophonate exhibits a significant inhibition of endothelial dependent platelet aggregation. The molecular mechanism of alendronate (ALN) on leukocyte adhesion depends on the regulation of the expression of cell adhesion related genes (VCAM-1; ICAM-1); meanwhile the antiplatelet activity is associated with the effect of the drug on nitric oxide production. On vascular smooth muscle cells, the drug exhibits ability to decrease osteogenic transdifferentiation and extracellular matrix mineralization. When vascular smooth muscle cells were cultured in osteogenic medium for 21 days, they exhibited an upregulation of calcification markers (RUNX2 and TNAP), high alkaline phosphatase activity and a great amount of mineralization nodules. ALN treatment significantly down-regulates mRNA levels of osteoblasts markers; diminishes alkaline phosphatase activity and reduces the extracellular calcium deposition. The effect of ALN on vascular cells differs from its own bone action. On calvarial osteoblasts ALN induces cell proliferation, enhances alkaline phosphatase activity, and increases mineralization, but does not affect nitric oxide synthesis. Our results support the hypothesis that ALN is an active drug at vascular level that regulates key processes involved in vascular pathogenesis through a direct action on vessel cells. Fil: Cutini, Pablo Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina Fil: Rauschemberger, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina Fil: Sandoval, Marisa Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina Fil: Massheimer, Virginia Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina |
description |
In this work we investigate whether, despite the procalcific action of alendronate on bone, the drug would be able to regulate in vitro the main cellular events that take part in atherosclerotic lesion generation. Using endothelial cell cultures we showed that Alendronate (1–50 μM) acutely enhances nitric oxide production (10–30 min). This stimulatory action of the bisphosphonate involves the participation of MAPK signaling transduction pathway. Under inflammatory stress, the drug reduces monocytes and platelets interactions with endothelial cells induced by lipopolysaccharide. Indeed the bisphophonate exhibits a significant inhibition of endothelial dependent platelet aggregation. The molecular mechanism of alendronate (ALN) on leukocyte adhesion depends on the regulation of the expression of cell adhesion related genes (VCAM-1; ICAM-1); meanwhile the antiplatelet activity is associated with the effect of the drug on nitric oxide production. On vascular smooth muscle cells, the drug exhibits ability to decrease osteogenic transdifferentiation and extracellular matrix mineralization. When vascular smooth muscle cells were cultured in osteogenic medium for 21 days, they exhibited an upregulation of calcification markers (RUNX2 and TNAP), high alkaline phosphatase activity and a great amount of mineralization nodules. ALN treatment significantly down-regulates mRNA levels of osteoblasts markers; diminishes alkaline phosphatase activity and reduces the extracellular calcium deposition. The effect of ALN on vascular cells differs from its own bone action. On calvarial osteoblasts ALN induces cell proliferation, enhances alkaline phosphatase activity, and increases mineralization, but does not affect nitric oxide synthesis. Our results support the hypothesis that ALN is an active drug at vascular level that regulates key processes involved in vascular pathogenesis through a direct action on vessel cells. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016-11 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/57353 Cutini, Pablo Hernan; Rauschemberger, María Belén; Sandoval, Marisa Julia; Massheimer, Virginia Laura; Vascular action of bisphosphonates: In vitro effect of alendronate on the regulation of cellular events involved in vessel pathogenesis; Academic Press Ltd - Elsevier Science Ltd; Journal of Molecular and Cellular Cardiology; 100; 11-2016; 83-92 0022-2828 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/57353 |
identifier_str_mv |
Cutini, Pablo Hernan; Rauschemberger, María Belén; Sandoval, Marisa Julia; Massheimer, Virginia Laura; Vascular action of bisphosphonates: In vitro effect of alendronate on the regulation of cellular events involved in vessel pathogenesis; Academic Press Ltd - Elsevier Science Ltd; Journal of Molecular and Cellular Cardiology; 100; 11-2016; 83-92 0022-2828 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0022282816303170 info:eu-repo/semantics/altIdentifier/doi/10.1016/j.yjmcc.2016.08.017 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Academic Press Ltd - Elsevier Science Ltd |
publisher.none.fl_str_mv |
Academic Press Ltd - Elsevier Science Ltd |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
reponame_str |
CONICET Digital (CONICET) |
collection |
CONICET Digital (CONICET) |
instname_str |
Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.name.fl_str_mv |
CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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1842268945833263104 |
score |
13.13397 |