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
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/57353
Acceder
id CONICETDig_c94fcef13e176a5a20e65c5c2657a940
oai_identifier_str oai:ri.conicet.gov.ar:11336/57353
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling 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 Técnicas2025-09-29T09:42:24Zoai: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:34982025-09-29 09:42:24.872CONICET 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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score 13.069144

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