Beneficial role of alendronate on cellular and molecular processes involved in calcification/vascular remodeling

Autores
Cutini, Pablo Hernan; Rauschemberger, María Belén; Massheimer, Virginia Laura
Año de publicación
2017
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
The genesis of the atheromatous lesion involves the interaction of monocytes and platelets with the endothelium. Finally, vascular calcification takes place through vascular smooth muscle cells (VSMC) transdifferentiation to bone lineage. The impact of bisphosphonates (BP) on cardiovascular diseases remains unknown. The aim of this study was to investigate the role of the BP alendronate (ALN) in cellular and molecular processes involved in vascular disease. Murine cultures cells were used: a) endothelial cells (EC); b) VSMC; c) VSMC induced to osteoblastic transdifferentiation (VSMC-OB) in osteogenic medium (β-glicerolfostato 5 mM; CaCl2 and 4 mM). The effect of ALN on platelet adhesion (PAd) and aggregation (PAg) was investigated. Under basal conditions ALN partially reduced PAd (20–35%; ALN 1–10 μM; p<0.01). The stimulus induced by LPS was partially reduced in the presence of the BP (22–33%; ALN 1–10 μM; p<0.02). We found that ALN markedly inhibited PAg compared with control (56%; ALN 10 μM; p<0.05). Both antiplatelet effects evoked by ALN were reversed in the presence of L-NAME, an inhibitor of nitric oxide synthase. Monocyte adhesion to EC depends on the expression of adhesion molecules. ALN treatment significantly prevents the enhancement of ICAM-1 and VCAM-1 mRNA levels induced by LPS. On VSMC-OB, ALN markedly reduce the expression of RUNX2 and TNAP, showed a significant diminution in FAL activity (9–29%; ALN 1–10 μM; p<0.02), as well as in extracellular calcium deposition (341 ± 33 vs 225 ± 24 μg/mg prot.; control vs ALN 5 μM; p<0.05). In summary, the results suggest that ALN is an active drug at vascular level with potential beneficial effects on processes that compromise the vascular architecture.
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: 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
1º Congreso Argentino de Osteología - XXXIII Reunión Anual de la AAOMM - XII Congreso Argentino de Osteoporosis (CAO)
Ciudad Autónoma de Buenos Aires
Argentina
Asociación Argentina de Osteología y Metabolismo Mineral
Sociedad Argentina de Osteoporois
Materia
ALENDRONATE
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:11336/235027
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/235027
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Beneficial role of alendronate on cellular and molecular processes involved in calcification/vascular remodelingCutini, Pablo HernanRauschemberger, María BelénMassheimer, Virginia LauraALENDRONATEVASCULARCALCIFICATIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The genesis of the atheromatous lesion involves the interaction of monocytes and platelets with the endothelium. Finally, vascular calcification takes place through vascular smooth muscle cells (VSMC) transdifferentiation to bone lineage. The impact of bisphosphonates (BP) on cardiovascular diseases remains unknown. The aim of this study was to investigate the role of the BP alendronate (ALN) in cellular and molecular processes involved in vascular disease. Murine cultures cells were used: a) endothelial cells (EC); b) VSMC; c) VSMC induced to osteoblastic transdifferentiation (VSMC-OB) in osteogenic medium (β-glicerolfostato 5 mM; CaCl2 and 4 mM). The effect of ALN on platelet adhesion (PAd) and aggregation (PAg) was investigated. Under basal conditions ALN partially reduced PAd (20–35%; ALN 1–10 μM; p<0.01). The stimulus induced by LPS was partially reduced in the presence of the BP (22–33%; ALN 1–10 μM; p<0.02). We found that ALN markedly inhibited PAg compared with control (56%; ALN 10 μM; p<0.05). Both antiplatelet effects evoked by ALN were reversed in the presence of L-NAME, an inhibitor of nitric oxide synthase. Monocyte adhesion to EC depends on the expression of adhesion molecules. ALN treatment significantly prevents the enhancement of ICAM-1 and VCAM-1 mRNA levels induced by LPS. On VSMC-OB, ALN markedly reduce the expression of RUNX2 and TNAP, showed a significant diminution in FAL activity (9–29%; ALN 1–10 μM; p<0.02), as well as in extracellular calcium deposition (341 ± 33 vs 225 ± 24 μg/mg prot.; control vs ALN 5 μM; p<0.05). In summary, the results suggest that ALN is an active drug at vascular level with potential beneficial effects on processes that compromise the vascular architecture.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: 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; Argentina1º Congreso Argentino de Osteología - XXXIII Reunión Anual de la AAOMM - XII Congreso Argentino de Osteoporosis (CAO)Ciudad Autónoma de Buenos AiresArgentinaAsociación Argentina de Osteología y Metabolismo MineralSociedad Argentina de OsteoporoisElsevierRoland, Baron2017info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/235027Beneficial role of alendronate on cellular and molecular processes involved in calcification/vascular remodeling; 1º Congreso Argentino de Osteología - XXXIII Reunión Anual de la AAOMM - XII Congreso Argentino de Osteoporosis (CAO); Ciudad Autónoma de Buenos Aires; Argentina; 2016; 302-3021873-27638756-3282CONICET DigitalCONICETenghttps://www.gador.com.ar/congresos/aaomm-sao-2016-xxxiii-reunion-anual-aaomm-xii-congreso-argentino-osteoporosis-cao-2016/info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bone.2017.03.021info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S875632821730090XNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:17:09Zoai:ri.conicet.gov.ar:11336/235027instacron: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 10:17:10.272CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Beneficial role of alendronate on cellular and molecular processes involved in calcification/vascular remodeling
title Beneficial role of alendronate on cellular and molecular processes involved in calcification/vascular remodeling
spellingShingle Beneficial role of alendronate on cellular and molecular processes involved in calcification/vascular remodeling
Cutini, Pablo Hernan
ALENDRONATE
VASCULAR
CALCIFICATION
title_short Beneficial role of alendronate on cellular and molecular processes involved in calcification/vascular remodeling
title_full Beneficial role of alendronate on cellular and molecular processes involved in calcification/vascular remodeling
title_fullStr Beneficial role of alendronate on cellular and molecular processes involved in calcification/vascular remodeling
title_full_unstemmed Beneficial role of alendronate on cellular and molecular processes involved in calcification/vascular remodeling
title_sort Beneficial role of alendronate on cellular and molecular processes involved in calcification/vascular remodeling
dc.creator.none.fl_str_mv Cutini, Pablo Hernan
Rauschemberger, María Belén
Massheimer, Virginia Laura
author Cutini, Pablo Hernan
author_facet Cutini, Pablo Hernan
Rauschemberger, María Belén
Massheimer, Virginia Laura
author_role author
author2 Rauschemberger, María Belén
Massheimer, Virginia Laura
author2_role author
author
dc.contributor.none.fl_str_mv Roland, Baron
dc.subject.none.fl_str_mv ALENDRONATE
VASCULAR
CALCIFICATION
topic ALENDRONATE
VASCULAR
CALCIFICATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The genesis of the atheromatous lesion involves the interaction of monocytes and platelets with the endothelium. Finally, vascular calcification takes place through vascular smooth muscle cells (VSMC) transdifferentiation to bone lineage. The impact of bisphosphonates (BP) on cardiovascular diseases remains unknown. The aim of this study was to investigate the role of the BP alendronate (ALN) in cellular and molecular processes involved in vascular disease. Murine cultures cells were used: a) endothelial cells (EC); b) VSMC; c) VSMC induced to osteoblastic transdifferentiation (VSMC-OB) in osteogenic medium (β-glicerolfostato 5 mM; CaCl2 and 4 mM). The effect of ALN on platelet adhesion (PAd) and aggregation (PAg) was investigated. Under basal conditions ALN partially reduced PAd (20–35%; ALN 1–10 μM; p<0.01). The stimulus induced by LPS was partially reduced in the presence of the BP (22–33%; ALN 1–10 μM; p<0.02). We found that ALN markedly inhibited PAg compared with control (56%; ALN 10 μM; p<0.05). Both antiplatelet effects evoked by ALN were reversed in the presence of L-NAME, an inhibitor of nitric oxide synthase. Monocyte adhesion to EC depends on the expression of adhesion molecules. ALN treatment significantly prevents the enhancement of ICAM-1 and VCAM-1 mRNA levels induced by LPS. On VSMC-OB, ALN markedly reduce the expression of RUNX2 and TNAP, showed a significant diminution in FAL activity (9–29%; ALN 1–10 μM; p<0.02), as well as in extracellular calcium deposition (341 ± 33 vs 225 ± 24 μg/mg prot.; control vs ALN 5 μM; p<0.05). In summary, the results suggest that ALN is an active drug at vascular level with potential beneficial effects on processes that compromise the vascular architecture.
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: 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
1º Congreso Argentino de Osteología - XXXIII Reunión Anual de la AAOMM - XII Congreso Argentino de Osteoporosis (CAO)
Ciudad Autónoma de Buenos Aires
Argentina
Asociación Argentina de Osteología y Metabolismo Mineral
Sociedad Argentina de Osteoporois
description The genesis of the atheromatous lesion involves the interaction of monocytes and platelets with the endothelium. Finally, vascular calcification takes place through vascular smooth muscle cells (VSMC) transdifferentiation to bone lineage. The impact of bisphosphonates (BP) on cardiovascular diseases remains unknown. The aim of this study was to investigate the role of the BP alendronate (ALN) in cellular and molecular processes involved in vascular disease. Murine cultures cells were used: a) endothelial cells (EC); b) VSMC; c) VSMC induced to osteoblastic transdifferentiation (VSMC-OB) in osteogenic medium (β-glicerolfostato 5 mM; CaCl2 and 4 mM). The effect of ALN on platelet adhesion (PAd) and aggregation (PAg) was investigated. Under basal conditions ALN partially reduced PAd (20–35%; ALN 1–10 μM; p<0.01). The stimulus induced by LPS was partially reduced in the presence of the BP (22–33%; ALN 1–10 μM; p<0.02). We found that ALN markedly inhibited PAg compared with control (56%; ALN 10 μM; p<0.05). Both antiplatelet effects evoked by ALN were reversed in the presence of L-NAME, an inhibitor of nitric oxide synthase. Monocyte adhesion to EC depends on the expression of adhesion molecules. ALN treatment significantly prevents the enhancement of ICAM-1 and VCAM-1 mRNA levels induced by LPS. On VSMC-OB, ALN markedly reduce the expression of RUNX2 and TNAP, showed a significant diminution in FAL activity (9–29%; ALN 1–10 μM; p<0.02), as well as in extracellular calcium deposition (341 ± 33 vs 225 ± 24 μg/mg prot.; control vs ALN 5 μM; p<0.05). In summary, the results suggest that ALN is an active drug at vascular level with potential beneficial effects on processes that compromise the vascular architecture.
publishDate 2017
dc.date.none.fl_str_mv 2017
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
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info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/235027
Beneficial role of alendronate on cellular and molecular processes involved in calcification/vascular remodeling; 1º Congreso Argentino de Osteología - XXXIII Reunión Anual de la AAOMM - XII Congreso Argentino de Osteoporosis (CAO); Ciudad Autónoma de Buenos Aires; Argentina; 2016; 302-302
1873-2763
8756-3282
CONICET Digital
CONICET
url http://hdl.handle.net/11336/235027
identifier_str_mv Beneficial role of alendronate on cellular and molecular processes involved in calcification/vascular remodeling; 1º Congreso Argentino de Osteología - XXXIII Reunión Anual de la AAOMM - XII Congreso Argentino de Osteoporosis (CAO); Ciudad Autónoma de Buenos Aires; Argentina; 2016; 302-302
1873-2763
8756-3282
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv https://www.gador.com.ar/congresos/aaomm-sao-2016-xxxiii-reunion-anual-aaomm-xii-congreso-argentino-osteoporosis-cao-2016/
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bone.2017.03.021
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S875632821730090X
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
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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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