EL TRATAMIENTO ORAL CON METFORMINA PREVIENE SIGNOS TEMPRANOS DE ARTERIOESCLEROSIS AÓRTICA INDUCIDA POR AGE/RAGE EN RATAS CON SÍNDROME METABÓLICO.
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| Title: | EL TRATAMIENTO ORAL CON METFORMINA PREVIENE SIGNOS TEMPRANOS DE ARTERIOESCLEROSIS AÓRTICA INDUCIDA POR AGE/RAGE EN RATAS CON SÍNDROME METABÓLICO. |
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| Alternate Title: | ORAL TREATMENT WITH METFORMIN PREVENTS EARLY SIGNS OF AGE/RAGEINDUCED AORTIC ARTERIOSCLEROSIS IN RATS WITH METABOLIC SYNDROME. |
| Authors: | Streckwall, Lucas1, Martini, Nancy1, Sedlinsky, Claudia1, Schurman, León1, Gangoiti, María Virginia1, Desmond McCarthy, Antonio1 |
| Source: | Actualizaciones en Osteología. may-ago2025, Vol. 21 Issue 2, p150-167. 18p. |
| Subjects: | METFORMIN, METABOLIC syndrome, ARTERIAL calcification, RECEPTOR for advanced glycation end products (RAGE), ADVANCED glycation end-products, ARTERIOSCLEROSIS, MUSCLE cells, AMP-activated protein kinases |
| Abstract (English): | Introduction: Metabolic syndrome (MS) is associated with increased carbonyl stress, accumulation of advanced glycation end products (AGE), and induction of arterial calcifications (AC) through the osteoblastic transdifferentiation of vascular smooth muscle cells (VSMC). Metformin (MET) inhibits this transdifferentiation in vitro. We evaluated whether oral MET can prevent AC in an experimental model of MS. Materials and Methods: Young adult male Wistar rats were divided into two groups: one received water as the drinking source (C) and the other a 20% fructose solution (F). After two weeks, and for an additional four weeks, each group was subdivided, and MET (100 mg/kg/day) was added to the drinking water of one half (thus, M and FM). Metabolic and body parameters were measured. The aorta was dissected for histomorphometric and immunohistochemical analyses. Aortic VSMC were isolated to assess alkaline phosphatase (ALP) activity, collagen production, extracellular matrix mineralization, and gene expression of Runx2 and the receptor for AGE (RAGE). Results: Group F developed features consistent with MS, including increased adiposity, non-fasting hyperglycemia, dyslipidemia, and elevated serum fructosamine. Aortas from F animals showed a reduced elastic-to-muscular ratio, increased collagen content, AGE accumulation, and RAGE overexpression. VSMC from F rats displayed higher ALP activity, increased collagen production and mineralization, and elevated expression of Runx2 and RAGE. Cotreatment with MET prevented all these MS-induced alterations. In vitro, MET blocked AGE-induced RAGE upregulation by VSMC, an effect abolished by an AMP-activated protein kinase (AMPK) inhibitor. Conclusion: These findings indicate that oral MET treatment attenuates extracellular glycation, AGE/RAGE activation, and vascular remodeling associated with experimental MS. [ABSTRACT FROM AUTHOR] |
| Abstract (Spanish): | Introducción: El síndrome metabólico (SM) se asocia al aumento de estrés carbonílico y productos de glicación avanzada (AGE) y favorece la calcificación arterial (CA) por transdiferenciación osteogénica de células de músculo liso vascular (CMLV). La metformina (MET) inhibe esa transdiferenciación in vitro. Evaluamos si MET oral previene CA en un modelo experimental de SM. Materiales y métodos: Ratas Wistar macho jóvenes adultos fueron separadas en dos grupos: uno recibió agua como bebida (C) y el otro una solución 20% de fructosa (F). Tras dos semanas, y por cuatro más, cada grupo original se dividió, agregándose MET (100 mg/ kg/día) a la bebida de la mitad de cada grupo (así, M y FM). Se midieron parámetros metabólicos y corporales. La aorta se disecó para análisis histomorfométrico e inmunohistoquímico. Se aislaron CMLV aórticas para evaluar la actividad de fosfatasa alcalina (FAL), producción de colágeno, mineralización extracelular y expresión génica de Runx2 y receptor para AGE (RAGE). Resultados: El grupo F desarrolló rasgos compatibles con SM: mayor adiposidad, hiperglucemia, dislipemia y aumento de fructosamina. Las aortas de F evidenciaron reducción de la relación capa elástica/muscular, aumento de colágeno, acumulación de AGE y sobreexpresión de RAGE. Las CMLV de F mostraron mayor actividad FAL, incremento de colágeno y mineralización, junto a aumento de expresión de Runx2 y RAGE. El cotratamiento con MET previno estas alteraciones. In vitro, MET bloqueó la inducción de RAGE por AGE; efecto que se anuló con un inhibidor de la proteína quinasa activada por AMP (AMPK). Conclusión: Estos resultados indican que MET atenúa la glicación extracelular, la activación AGE/RAGE y el remodelado vascular asociado al SM experimental. [ABSTRACT FROM AUTHOR] |
| Copyright of Actualizaciones en Osteología is the property of Asociacion Argentina de Osteologia y Metabolismo Mineral and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | MedicLatina |
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| Header | DbId: lth DbLabel: MedicLatina An: 193637342 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: EL TRATAMIENTO ORAL CON METFORMINA PREVIENE SIGNOS TEMPRANOS DE ARTERIOESCLEROSIS AÓRTICA INDUCIDA POR AGE/RAGE EN RATAS CON SÍNDROME METABÓLICO. – Name: TitleAlt Label: Alternate Title Group: TiAlt Data: ORAL TREATMENT WITH METFORMIN PREVENTS EARLY SIGNS OF AGE/RAGEINDUCED AORTIC ARTERIOSCLEROSIS IN RATS WITH METABOLIC SYNDROME. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Streckwall%2C+Lucas%22">Streckwall, Lucas</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Martini%2C+Nancy%22">Martini, Nancy</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Sedlinsky%2C+Claudia%22">Sedlinsky, Claudia</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Schurman%2C+León%22">Schurman, León</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Gangoiti%2C+María+Virginia%22">Gangoiti, María Virginia</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Desmond+McCarthy%2C+Antonio%22">Desmond McCarthy, Antonio</searchLink><relatesTo>1</relatesTo> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Actualizaciones+en+Osteología%22">Actualizaciones en Osteología</searchLink>. may-ago2025, Vol. 21 Issue 2, p150-167. 18p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22METFORMIN%22">METFORMIN</searchLink><br /><searchLink fieldCode="DE" term="%22METABOLIC+syndrome%22">METABOLIC syndrome</searchLink><br /><searchLink fieldCode="DE" term="%22ARTERIAL+calcification%22">ARTERIAL calcification</searchLink><br /><searchLink fieldCode="DE" term="%22RECEPTOR+for+advanced+glycation+end+products+%28RAGE%29%22">RECEPTOR for advanced glycation end products (RAGE)</searchLink><br /><searchLink fieldCode="DE" term="%22ADVANCED+glycation+end-products%22">ADVANCED glycation end-products</searchLink><br /><searchLink fieldCode="DE" term="%22ARTERIOSCLEROSIS%22">ARTERIOSCLEROSIS</searchLink><br /><searchLink fieldCode="DE" term="%22MUSCLE+cells%22">MUSCLE cells</searchLink><br /><searchLink fieldCode="DE" term="%22AMP-activated+protein+kinases%22">AMP-activated protein kinases</searchLink> – Name: Abstract Label: Abstract (English) Group: Ab Data: Introduction: Metabolic syndrome (MS) is associated with increased carbonyl stress, accumulation of advanced glycation end products (AGE), and induction of arterial calcifications (AC) through the osteoblastic transdifferentiation of vascular smooth muscle cells (VSMC). Metformin (MET) inhibits this transdifferentiation in vitro. We evaluated whether oral MET can prevent AC in an experimental model of MS. Materials and Methods: Young adult male Wistar rats were divided into two groups: one received water as the drinking source (C) and the other a 20% fructose solution (F). After two weeks, and for an additional four weeks, each group was subdivided, and MET (100 mg/kg/day) was added to the drinking water of one half (thus, M and FM). Metabolic and body parameters were measured. The aorta was dissected for histomorphometric and immunohistochemical analyses. Aortic VSMC were isolated to assess alkaline phosphatase (ALP) activity, collagen production, extracellular matrix mineralization, and gene expression of Runx2 and the receptor for AGE (RAGE). Results: Group F developed features consistent with MS, including increased adiposity, non-fasting hyperglycemia, dyslipidemia, and elevated serum fructosamine. Aortas from F animals showed a reduced elastic-to-muscular ratio, increased collagen content, AGE accumulation, and RAGE overexpression. VSMC from F rats displayed higher ALP activity, increased collagen production and mineralization, and elevated expression of Runx2 and RAGE. Cotreatment with MET prevented all these MS-induced alterations. In vitro, MET blocked AGE-induced RAGE upregulation by VSMC, an effect abolished by an AMP-activated protein kinase (AMPK) inhibitor. Conclusion: These findings indicate that oral MET treatment attenuates extracellular glycation, AGE/RAGE activation, and vascular remodeling associated with experimental MS. [ABSTRACT FROM AUTHOR] – Name: Abstract Label: Abstract (Spanish) Group: Ab Data: Introducción: El síndrome metabólico (SM) se asocia al aumento de estrés carbonílico y productos de glicación avanzada (AGE) y favorece la calcificación arterial (CA) por transdiferenciación osteogénica de células de músculo liso vascular (CMLV). La metformina (MET) inhibe esa transdiferenciación in vitro. Evaluamos si MET oral previene CA en un modelo experimental de SM. Materiales y métodos: Ratas Wistar macho jóvenes adultos fueron separadas en dos grupos: uno recibió agua como bebida (C) y el otro una solución 20% de fructosa (F). Tras dos semanas, y por cuatro más, cada grupo original se dividió, agregándose MET (100 mg/ kg/día) a la bebida de la mitad de cada grupo (así, M y FM). Se midieron parámetros metabólicos y corporales. La aorta se disecó para análisis histomorfométrico e inmunohistoquímico. Se aislaron CMLV aórticas para evaluar la actividad de fosfatasa alcalina (FAL), producción de colágeno, mineralización extracelular y expresión génica de Runx2 y receptor para AGE (RAGE). Resultados: El grupo F desarrolló rasgos compatibles con SM: mayor adiposidad, hiperglucemia, dislipemia y aumento de fructosamina. Las aortas de F evidenciaron reducción de la relación capa elástica/muscular, aumento de colágeno, acumulación de AGE y sobreexpresión de RAGE. Las CMLV de F mostraron mayor actividad FAL, incremento de colágeno y mineralización, junto a aumento de expresión de Runx2 y RAGE. El cotratamiento con MET previno estas alteraciones. In vitro, MET bloqueó la inducción de RAGE por AGE; efecto que se anuló con un inhibidor de la proteína quinasa activada por AMP (AMPK). Conclusión: Estos resultados indican que MET atenúa la glicación extracelular, la activación AGE/RAGE y el remodelado vascular asociado al SM experimental. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Actualizaciones en Osteología is the property of Asociacion Argentina de Osteologia y Metabolismo Mineral and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Languages: – Code: spa Text: Spanish PhysicalDescription: Pagination: PageCount: 18 StartPage: 150 Subjects: – SubjectFull: METFORMIN Type: general – SubjectFull: METABOLIC syndrome Type: general – SubjectFull: ARTERIAL calcification Type: general – SubjectFull: RECEPTOR for advanced glycation end products (RAGE) Type: general – SubjectFull: ADVANCED glycation end-products Type: general – SubjectFull: ARTERIOSCLEROSIS Type: general – SubjectFull: MUSCLE cells Type: general – SubjectFull: AMP-activated protein kinases Type: general Titles: – TitleFull: EL TRATAMIENTO ORAL CON METFORMINA PREVIENE SIGNOS TEMPRANOS DE ARTERIOESCLEROSIS AÓRTICA INDUCIDA POR AGE/RAGE EN RATAS CON SÍNDROME METABÓLICO. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Streckwall, Lucas – PersonEntity: Name: NameFull: Martini, Nancy – PersonEntity: Name: NameFull: Sedlinsky, Claudia – PersonEntity: Name: NameFull: Schurman, León – PersonEntity: Name: NameFull: Gangoiti, María Virginia – PersonEntity: Name: NameFull: Desmond McCarthy, Antonio IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 05 Text: may-ago2025 Type: published Y: 2025 Identifiers: – Type: issn-print Value: 16698975 Numbering: – Type: volume Value: 21 – Type: issue Value: 2 Titles: – TitleFull: Actualizaciones en Osteología Type: main |
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