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8. Soluble α-klotho and heparin modulate the pathologic cardiac actions of fibroblast growth factor 23 in chronic kidney disease

Author

Yanucil, Christopher, Kentrup, Dominik, Campos, Isaac, Czaya, Brian, Heitman, Kylie, Westbrook, David, Osis, Gunars, Grabner, Alexander, Wende, Adam R., Vallejo, Julian, Wacker, Michael J., Navarro-Garcia, Jose Alberto, Ruiz-Hurtado, Gema, Zhang, Fuming, Song, Yuefan, Linhardt, Robert J., White, Kenneth, Kapiloff, Michael S., and Faul, Christian

Published
2022
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9. Specialized Proresolving Mediators Protect Against Experimental Autoimmune Myocarditis by Modulating Ca2+ Handling and NRF2 Activation

Author

Val-Blasco, Almudena, Prieto, Patricia, Jaén, Rafael Iñigo, Gil-Fernández, Marta, Pajares, Marta, Domenech, Nieves, Terrón, Verónica, Tamayo, María, Jorge, Inmaculada, Vázquez, Jesús, Bueno-Sen, Andrea, Vallejo-Cremades, María Teresa, Pombo-Otero, Jorge, Sanchez-García, Sergio, Ruiz-Hurtado, Gema, Gómez, Ana María, Zaragoza, Carlos, Crespo-Leiro, María Generosa, López-Collazo, Eduardo, Cuadrado, Antonio, Delgado, Carmen, Boscá, Lisardo, and Fernández-Velasco, María

Published
2022
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10. Artificial Intelligence–Derived Risk Prediction: A Novel Risk Calculator Using Office and Ambulatory Blood Pressure.

Author

Guimarães, Pedro, Keller, Andreas, Böhm, Michael, Lauder, Lucas, Fehlmann, Tobias, Ruilope, Luis M., Vinyoles, Ernest, Gorostidi, Manuel, Segura, Julián, Ruiz-Hurtado, Gema, Staplin, Natalie, Williams, Bryan, de la Sierra, Alejandro, and Mahfoud, Felix

Abstract

BACKGROUND: Quantification of total cardiovascular risk is essential for individualizing hypertension treatment. This study aimed to develop and validate a novel, machine-learning–derived model to predict cardiovascular mortality risk using office blood pressure (OBP) and ambulatory blood pressure (ABP). METHODS: The performance of the novel risk score was compared with existing risk scores, and the possibility of predicting ABP phenotypes utilizing clinical variables was assessed. Using data from 59 124 patients enrolled in the Spanish ABP Monitoring registry, machine-learning approaches (logistic regression, gradient-boosted decision trees, and deep neural networks) and stepwise forward feature selection were used. RESULTS: For the prediction of cardiovascular mortality, deep neural networks yielded the highest clinical performance. The novel mortality prediction models using OBP and ABP outperformed other risk scores. The area under the curve achieved by the novel approach, already when using OBP variables, was significantly higher when compared with the area under the curve of the Framingham risk score, Systemic Coronary Risk Estimation 2, and Atherosclerotic Cardiovascular Disease score. However, the prediction of cardiovascular mortality with ABP instead of OBP data significantly increased the area under the curve (0.870 versus 0.865; P =3.61×10−28), accuracy, and specificity, respectively. The prediction of ABP phenotypes (ie, white-coat, ambulatory, and masked hypertension) using clinical characteristics was limited. CONCLUSIONS: The receiver operating characteristic curves for cardiovascular mortality using ABP and OBP with deep neural network models outperformed all other risk metrics, indicating the potential for improving current risk scores by applying state-of-the-art machine learning approaches. The prediction of cardiovascular mortality using ABP data led to a significant increase in area under the curve and performance metrics. [ABSTRACT FROM AUTHOR]

Published
2025
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11. Chronic kidney disease promotes atrial fibrillation via inflammasome pathway activation

Author

Song, Jia, Navarro-Garcia, Jose Alberto, Wu, Jiao, Saljic, Arnela, Abu-Taha, Issam, Li, Luge, Lahiri, Satadru K., Keefe, Joshua A., Aguilar-Sanchez, Yuriana, Moore, Oliver M., Yuan, Yue, Wang, Xiaolei, Kamler, Markus, Mitch, William E., Ruiz-Hurtado, Gema, Hu, Zhaoyong, Thomas, Sandhya S., Dobrev, Dobromir, Wehrens, Xander H.T., and Li, Na

Subjects
Complications and side effects, Development and progression, Risk factors, Health aspects, Inflammasomes -- Health aspects, Atrial fibrillation -- Development and progression -- Risk factors, Cellular signal transduction -- Health aspects, Chronic kidney failure -- Complications and side effects
Abstract

Introduction Atrial fibrillation (AF) is the most commonly diagnosed cardiac arrhythmia, with a high prevalence worldwide (1, 2). AF significantly affects the quality of life, as it is associated with [...], Chronic kidney disease (CKD) is associated with a higher risk of atrial fibrillation (AF). The mechanistic link between CKD and AF remains elusive. IL-1[beta], a main effector of NLR family pyrin domain-containing 3 (NLRP3) inflammasome activation, is a key modulator of conditions associated with inflammation, such as AF and CKD. Circulating IL-1[beta] levels were elevated patients with CKD who had AF (versus patients with CKD in sinus rhythm). Moreover, NLRP3 activity was enhanced in atria of patients with CKD. To elucidate the role of NLRP3/IL- 1[beta] signaling in the pathogenesis of CKD-induced AF, [Nlrp3.sup.-/-] and WT mice were subjected to a 2-stage subtotal nephrectomy protocol to induce CKD. Four weeks after surgery, IL-1[beta] levels in serum and atrial tissue were increased in WT CKD (WT-CKD) mice versus sham-operated WT (WT-sham) mice. The increased susceptibility to pacing-induced AF and the longer AF duration in WT-CKD mice were associated with an abbreviated atrial effective refractory period, enlarged atria, and atrial fibrosis. Genetic inhibition of NLRP3 in [Nlrp3.sup.-/-] mice or neutralizing anti-IL- 1[beta] antibodies effectively reduced IL- 1[beta] levels, normalized left atrial dimensions, and reduced fibrosis and the incidence of AF. These data suggest that CKD creates a substrate for AF development by activating the NLRP3 inflammasome in atria, which is associated with structural and electrical remodeling. Neutralizing IL-1[beta] antibodies may be beneficial in preventing CKD-induced AF.

Published
2023
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12. Interplay between mineral bone disorder and cardiac damage in acute kidney injury: from Ca2+ mishandling and preventive role of Klotho in mice to its potential mortality prediction in human

Author

GONZÁLEZ-LAFUENTE, LAURA, NAVARRO-GARCÍA, JOSÉ ALBERTO, RODRÍGUEZ-SÁNCHEZ, ELENA, ACEVES-RIPOLL, JENNIFER, POVEDA, JONAY, VÁZQUEZ-SÁNCHEZ, SARA, MERCADO-GARCÍA, ELISA, FERNÁNDEZ-VELASCO, MARÍA, KURO-O, MAKOTO, LIAÑO, FERNANDO, RUILOPE, LUIS M., and RUIZ-HURTADO, GEMA

Published
2022
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13. The anti-aging factor Klotho protects against acquired long QT syndrome induced by uremia and promoted by fibroblast growth factor 23

Author

Navarro-García, José Alberto, Salguero-Bodes, Rafael, González-Lafuente, Laura, Martín-Nunes, Laura, Rodríguez-Sánchez, Elena, Bada-Bosch, Teresa, Hernández, Eduardo, Mérida-Herrero, Evangelina, Praga, Manuel, Solís, Jorge, Arribas, Fernando, Bueno, Héctor, Kuro-O, Makoto, Fernández-Velasco, María, Ruilope, Luis Miguel, Delgado, Carmen, and Ruiz-Hurtado, Gema

Published
2022
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14. Donor Dependent Variations in Systemic Oxidative Stress and Their Association with One-Year Graft Outcomes In Kidney Transplantation

Author

Rodriguez-Sanchez, Elena, primary, Aceves-Ripoll, Jennifer, additional, Mercado-García, Elisa, additional, Navarro-García, José A., additional, Andrés, Amado, additional, Aguado, José M, additional, Segura, Julián, additional, Ruilope, Luis M., additional, Fernández-Ruiz, Mario, additional, and Ruiz-Hurtado, Gema, additional

Published
2024
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16. Glucose-Lowering Drugs and Primary Prevention of Chronic Kidney Disease in Type 2 Diabetes Patients: A Real-World Primary Care Study.

Author

Rodríguez-Miguel, Antonio, Fernández-Fernández, Beatriz, Ortiz, Alberto, Gil, Miguel, Rodríguez-Martín, Sara, Ruiz-Hurtado, Gema, Fernández-Antón, Encarnación, Ruilope, Luis M., and de Abajo, Francisco J.

Subjects
GLUCAGON-like peptide-1 receptor, TYPE 2 diabetes, GLUCAGON-like peptide-1 agonists, CHRONIC kidney failure, PEOPLE with diabetes
Abstract

Background/Objectives: The burden of chronic kidney disease (CKD) is increasing, as is the prevalence of type 2 diabetes mellitus (T2DM). Post-hoc analyses of clinical trials support that sodium–glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptors agonists (GLP-1RAs) prevent CKD in T2DM patients. Methods: We used the Spanish primary care database BIFAP to perform a retrospective cohort study with a nested case-control analysis to assess the incidence, risk factors, and the effect of glucose-lowering drugs (GLDs) on the primary prevention of CKD. Results: From a cohort of 515,701 T2DM subjects (2.75 million person-years), we found 89,075 incident CKD cases, yielding an overall incidence rate (95%CI) of 324.3 (322.1–326.5) per 10,000 person-years. In the nested case–control analysis, gout, hyperuricemia, and hyperkalemia were the factors showing the highest AORs. Long-term users (≥3 years) of GLP1-RAs and SGLT-2i, compared to other GLDs, showed a decreased risk for CKD (AOR = 0.85; 95%CI: 0.73–0.99 and AOR = 0.89; 95%CI: 0.74–1.08, respectively), and for incident CKD at KDIGO stages G3-G5 (AOR = 0.72; 95%CI: 0.56–0.94 and AOR = 0.64; 95%CI: 0.46–0.91, respectively). Conclusions: In a real-world primary care setting, the long-term use of GLP-1RAs and SGLT-2i, but not other GLDs, appeared to decrease the risk of incident CKD in T2DM, supporting a role in primary prevention of CKD. [ABSTRACT FROM AUTHOR]

Published
2024
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17. Urinary extracellular vesicles as a monitoring tool for renal damage in patients not meeting criteria for chronic kidney disease.

Author

Anfaiha‐Sanchez, Miriam, Santiago‐Hernandez, Aranzazu, Lopez, Juan Antonio, Lago‐Baameiro, Nerea, Pardo, Maria, Martin‐Blazquez, Ariadna, Vazquez, Jesus, Ruiz‐Hurtado, Gema, Barderas, Maria G., Segura, Julian, Ruilope, Luis M., Martin‐Lorenzo, Marta, and Alvarez‐Llamas, Gloria

Subjects
FATTY acid-binding proteins, DISEASE risk factors, CHRONIC kidney failure, EXTRACELLULAR vesicles, MEMBRANE proteins
Abstract

Background: Current definition of chronic kidney disease (CKD) identifies only advanced stages, but effective management demands early detection. Urinary albumin‐to‐creatinine ratio (ACR) 30 mg/g is a cut‐off point for CKD clinical diagnosis. Patients with lower values (normoalbuminuria) and eGFR > 60 mL/min/1.73 m2 are considered at no increased cardiorenal risk. However, higher incidence of renal function decline and cardiovascular events have been shown within the normoalbuminuria range. Novel subclinical indicators may help to identify higher‐risk patients. Urinary extracellular vesicles (uEVs) are sentinels of renal function non‐invasively. Here we aimed to approach the early assessment of cardiorenal risk by investigating the protein cargo of uEVs. Methods: Hypertensive patients were classified in control group (C) with ACR < 10 mg/g, and high‐normal group (HN) with ACR 10–30 mg/g. Isolated uEVs were characterized by western blotting and electron microscopy and the protein cargo was analyzed by untargeted proteomics (LC‐MS/MS) in a first discovery cohort. Protein confirmation was performed in a different cohort by ExoView. Immunohistochemistry of human kidney biopsies was also performed to evaluate the potential of uEVs to reflect renal damage. Results: HN albuminuria does not affect the uEVs concentration, size, or tetraspanin profile. Among >6200 uEVs proteins identified, 43 define a panel significantly altered in HN patients without variation in urine, mostly annotated in the tubule (39 out of 43). The tubular transporter long‐chain fatty acid transport protein 2 (SLC27A2) and the apical membrane protein amnionless (AMN) confirmed their alteration in HN patients evidencing impaired tubular reabsorption. SLC27A2 showed tubular expression and significantly reduced levels in patients with diagnostic criteria for CKD. Conclusions: Alterations in the EV‐mediated molecular profile are evident before pathological ACR levels are reached. Direct quantitation of SLC27A2 and AMN in uEVs helps identifying normoalbuminuric subjects with higher cardiorenal risk in early monitoring of CKD. [ABSTRACT FROM AUTHOR]

Published
2024
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20. Novel molecular plasma signatures on cardiovascular disease can stratify patients throughout life

Author

Corbacho-Alonso, Nerea, Baldán-Martín, Montserrat, López, Juan Antonio, Rodríguez-Sánchez, Elena, Martínez, Paula J., Mourino-Alvarez, Laura, Martin-Rojas, Tatiana, Sastre-Oliva, Tamara, Madruga, Felipe, Vázquez, Jesús, Padial, Luis R., Alvarez-Llamas, Gloria, Vivanco, Fernando, Ruiz-Hurtado, Gema, Ruilope, Luis M., and Barderas, Maria G.

Published
2020
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21. CHARACTERIZATION OF EARLY FUNCTIONAL, STRUCTURAL AND MOLECULAR ALTERATIONS IN A RAT MODEL OF CARDIORENAL SYNDROME TYPE IV: ROLE OF BMP-2

Author

Sanz-gómez, Marta, primary, Vázquez-sánchez, Sara, additional, Manzano-lista, Francisco Javier, additional, Palma-guzmán, Paloma, additional, Guzmán-aguayo, Ana Karen, additional, Bragado-garcía, Elvira, additional, Kreutz, Reinhold, additional, Ruiz-hurtado, Gema, additional, and Fernández-alfonso, María S., additional

Published
2024
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22. Artificial Intelligence–Derived Risk Prediction: A Novel Risk Calculator Using Office and Ambulatory Blood Pressure

Author

Guimarães, Pedro, primary, Keller, Andreas, additional, Böhm, Michael, additional, Lauder, Lucas, additional, Fehlmann, Tobias, additional, Ruilope, Luis M., additional, Vinyoles, Ernest, additional, Gorostidi, Manuel, additional, Segura, Julián, additional, Ruiz-Hurtado, Gema, additional, Staplin, Natalie, additional, Williams, Bryan, additional, de la Sierra, Alejandro, additional, and Mahfoud, Felix, additional

Published
2024
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24. Albumin redox modifications promote cell calcification reflecting the impact of oxidative status on aortic valve disease and atherosclerosis

Author

Sastre Oliva, Tamara, Corbacho Alonso, Nerea, Rodríguez Sánchez, Elena, Mercado García, Elisa, Perales Sánchez, Inés, Hernández Fernández, Germán, Juárez Alia, Cristina, Tejerina Sánchez, María Teresa, López Almodóvar, Luis F., Padial, Luis R, Sánchez, Pedro L., Martín Núñez, Ernesto, López Andrés, Natalia, Ruiz- Hurtado, Gema, Mourino Álvarez, Laura, Barderas, María G., Sastre Oliva, Tamara, Corbacho Alonso, Nerea, Rodríguez Sánchez, Elena, Mercado García, Elisa, Perales Sánchez, Inés, Hernández Fernández, Germán, Juárez Alia, Cristina, Tejerina Sánchez, María Teresa, López Almodóvar, Luis F., Padial, Luis R, Sánchez, Pedro L., Martín Núñez, Ernesto, López Andrés, Natalia, Ruiz- Hurtado, Gema, Mourino Álvarez, Laura, and Barderas, María G.

Abstract

Calcific aortic valve disease (CAVD) and coronary artery disease (CAD) are related cardiovascular diseases in which common mechanisms lead to tissue calcification. Oxidative stress plays a key role in these diseases and there is also evidence that the redox state of serum albumin exerts a significant influence on these conditions. To further explore this issue, we used multimarker scores (OxyScore and AntioxyScore) to assess the global oxidative status in patients with CAVD, with and without CAD, also evaluating their plasma thiol levels. In addition, valvular interstitial cells were treated with reduced, oxidized, and native albumin to study how this protein and its modifications affect cell calcification. The differences we found suggest that oxidative status is distinct in CAVD and CAD, with differences in redox markers and thiol levels. Importantly, the in vitro interstitial cell model revealed that modified albumin affects cell calcification, accelerating this process. Hence, we show here the importance of the redox system in the development of CAVD, emphasizing the relevance of multimarker scores, while also offering evidence of how the redox state of albumin influences vascular calcification. These data highlight the relevance of understanding the overall redox processes involved in these diseases, opening the door to new studies on antioxidants as potential therapies for these patients., Depto. de Farmacología y Toxicología, Fac. de Medicina, TRUE, pub

Published
2024

25. Albumin redox modifications promote cell calcification reflecting the impact of oxidative status on aortic valve disease and atherosclerosis

Author

Sastre-Oliva, Tamara, Corbacho-Alonso, Nerea, Rodríguez-Sanchez, Elena, Mercado-García, Elisa, Perales-Sánchez, Inés, Hernández-Fernández, Germán, Juárez-Alia, Cristina, Tejerina, Teresa, López-Almodóvar, Luis F., Padial, Luis R, Sánchez, Pedro L., Martín-Núñez, Ernesto, López-Andrés, Natalia, Ruiz-Hurtado, Gema, Mourino-Álvarez, Laura, Barderas, María G., Sastre-Oliva, Tamara, Corbacho-Alonso, Nerea, Rodríguez-Sanchez, Elena, Mercado-García, Elisa, Perales-Sánchez, Inés, Hernández-Fernández, Germán, Juárez-Alia, Cristina, Tejerina, Teresa, López-Almodóvar, Luis F., Padial, Luis R, Sánchez, Pedro L., Martín-Núñez, Ernesto, López-Andrés, Natalia, Ruiz-Hurtado, Gema, Mourino-Álvarez, Laura, and Barderas, María G.

Abstract

Calcific aortic valve disease (CAVD) and coronary artery disease (CAD) are related cardiovascular diseases in which common mechanisms lead to tissue calcification. Oxidative stress plays a key role in these diseases and there is also evidence that the redox state of serum albumin exerts a significant influence on these conditions. To further explore this issue, we used multimarker scores (OxyScore and AntioxyScore) to assess the global oxidative status in patients with CAVD, with and without CAD, also evaluating their plasma thiol levels. In addition, valvular interstitial cells were treated with reduced, oxidized, and native albumin to study how this protein and its modifications affect cell calcification. The differences we found suggest that oxidative status is distinct in CAVD and CAD, with differences in redox markers and thiol levels. Importantly, the in vitro interstitial cell model revealed that modified albumin affects cell calcification, accelerating this process. Hence, we show here the importance of the redox system in the development of CAVD, emphasizing the relevance of multimarker scores, while also offering evidence of how the redox state of albumin influences vascular calcification. These data highlight the relevance of understanding the overall redox processes involved in these diseases, opening the door to new studies on antioxidants as potential therapies for these patients., Depto. de Farmacología y Toxicología, Fac. de Medicina, TRUE, pub

Published
2024

26. Lifestyle interventions for the prevention and treatment of hypertension

Author

Valenzuela, Pedro L., Carrera-Bastos, Pedro, González Gálvez, Beatriz, Ruiz-Hurtado, Gema, Ordovas, José M., Ruilope, Luis M., Lucia, Alejandro, Valenzuela, Pedro L., Carrera-Bastos, Pedro, González Gálvez, Beatriz, Ruiz-Hurtado, Gema, Ordovas, José M., Ruilope, Luis M., and Lucia, Alejandro

Abstract

Hypertension affects approximately one third of the world's adult population and is a major cause of premature death despite considerable advances in pharmacological treatments. Growing evidence supports the use of lifestyle interventions for the prevention and adjuvant treatment of hypertension. In this Review, we provide a summary of the epidemiological research supporting the preventive and antihypertensive effects of major lifestyle interventions (regular physical exercise, body weight management and healthy dietary patterns), as well as other less traditional recommendations such as stress management and the promotion of adequate sleep patterns coupled with circadian entrainment. We also discuss the physiological mechanisms underlying the beneficial effects of these lifestyle interventions on hypertension, which include not only the prevention of traditional risk factors (such as obesity and insulin resistance) and improvements in vascular health through an improved redox and inflammatory status, but also reduced sympathetic overactivation and non-traditional mechanisms such as increased secretion of myokines., Depto. de Bioquímica y Biología Molecular, Fac. de Farmacia, TRUE, pub

Published
2024

34. Albumin Redox Modifications Promote Cell Calcification Reflecting the Impact of Oxidative Status on Aortic Valve Disease and Atherosclerosis

Author

Sastre-Oliva, Tamara, primary, Corbacho-Alonso, Nerea, additional, Rodriguez-Sanchez, Elena, additional, Mercado-García, Elisa, additional, Perales-Sanchez, Ines, additional, Hernandez-Fernandez, German, additional, Juarez-Alia, Cristina, additional, Tejerina, Teresa, additional, López-Almodóvar, Luis F., additional, Padial, Luis R., additional, Sánchez, Pedro L., additional, Martín-Núñez, Ernesto, additional, López-Andrés, Natalia, additional, Ruiz-Hurtado, Gema, additional, Mourino-Alvarez, Laura, additional, and Barderas, Maria G., additional

Published
2024
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35. Recombinant Klotho Administration Just after Myocardial Infarction Reduces Ischemic Injury and Arrhythmias by Blocking Intracellular Calcium Mishandling and CaMKII Activation

Author

Vázquez-Sánchez, Sara, primary, Blasco, Ana, additional, Corredoira, Pablo, additional, Cantolla, Paula, additional, Mercado-García, Elisa, additional, Rodríguez-Sánchez, Elena, additional, González-Lafuente, Laura, additional, Poveda, Jonay, additional, González-Moreno, Daniel, additional, Matutano, Andrea, additional, Peribañez, Sonia, additional, Volpe, Massimo, additional, Fernández-Velasco, María, additional, Ruilope, Luis, additional, and Ruiz-Hurtado, Gema, additional

Published
2024
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36. Early renal and vascular damage within the normoalbuminuria condition

Author

Santiago-Hernandez, Aranzazu, Martin-Lorenzo, Marta, Martínez, Paula J., Gómez-Serrano, María, Lopez, Juan Antonio, Cannata, Pablo, Esteban, Vanesa, Heredero, Angeles, Aldamiz-Echevarria, Gonzalo, Vázquez, Jesús, Ruiz-Hurtado, Gema, Barderas, Maria G., Segura, Julian, Ruilope, Luis M., and Alvarez-Llamas, Gloria

Published
2021
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40. Targeting the TWEAK–Fn14 pathway prevents dysfunction in cardiac calcium handling after acute kidney injury

Author

Poveda, Jonay, primary, González‐Lafuente, Laura, additional, Vázquez‐Sánchez, Sara, additional, Mercado‐García, Elisa, additional, Rodríguez‐Sánchez, Elena, additional, García‐Consuegra, Inés, additional, Sanz, Ana Belén, additional, Segura, Julián, additional, Fernández‐Velasco, María, additional, Liaño, Fernando, additional, Ruilope, Luis M, additional, and Ruiz‐Hurtado, Gema, additional

Published
2023
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41. Early Posttransplant Mobilization of Monocytic Myeloid-derived Suppressor Cell Correlates With Increase in Soluble Immunosuppressive Factors and Predicts Cancer in Kidney Recipients

Author

Utrero-Rico, Alberto, Laguna-Goya, Rocio, Cano-Romero, Francisco, Chivite-Lacaba, Marta, Gonzalez-Cuadrado, Cecilia, Rodríguez-Sánchez, Elena, Ruiz-Hurtado, Gema, Serrano, Antonio, Fernández-Ruiz, Mario, Justo, Iago, González, Esther, Andrés, Amado, and Paz-Artal, Estela

Published
2020
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44. Frequency and Prognosis of Treated Hypertensive Patients According to Prior and New Blood Pressure Goals: Post Hoc Analysis of the Spanish Ambulatory Blood Pressure Monitoring Registry

Author

Ruilope, Luis M., Ruiz-Hurtado, Gema, Barderas, María G., de la Cruz, Juan J., Lucia, Alejandro, de la Sierra, Alejandro, Gorostidi, Manuel, Vinyoles, Ernest, Segura, Julián, Solís, Jorge, Arribas, Fernando, García-Puig, Juan, Tamargo, Juan, O’Brien, Eoin, Volpe, Massimo, Whelton, Paul K., Williams, Bryan, and Banegas, José R.

Published
2019
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47. Global oxidative status is linked to calcific aortic stenosis: the differences due to diabetes mellitus and the effects of metformin

Author

Corbacho-Alonso, Nerea, Rodríguez-Sánchez, Elena, Sastre-Oliva, Tamara, Mercado-García, Elisa, Perales-Sánchez, Ines, Juarez-Alia, Cristina, López-Almodovar, Luis, Padial, Luis, Tejerina Sánchez, María Teresa, Mourino-Alvarez, Laura, Ruiz-Hurtado, Gema, Barderas, María, Corbacho-Alonso, Nerea, Rodríguez-Sánchez, Elena, Sastre-Oliva, Tamara, Mercado-García, Elisa, Perales-Sánchez, Ines, Juarez-Alia, Cristina, López-Almodovar, Luis, Padial, Luis, Tejerina Sánchez, María Teresa, Mourino-Alvarez, Laura, Ruiz-Hurtado, Gema, and Barderas, María

Abstract

Calcific aortic stenosis (CAS) and type 2 diabetes mellitus (T2DM) are related and often concomitant pathologies, accompanied by common comorbidities such as hypertension or dyslipidemia. Oxidative stress is one of the mechanisms that trigger CAS, and it can drive the vascular complications in T2DM. Metformin can inhibit oxidative stress, yet its effects have not been studied in the context of CAS. Here, we assessed the global oxidative status in plasma from patients with CAS, both alone and with T2DM (and under treatment with metformin), using multimarker scores of systemic oxidative damage (OxyScore) and antioxidant defense (AntioxyScore). The OxyScore was determined by measuring carbonyls, oxidized LDL (oxLDL), 8-hydroxy-20-deoxyguanosine (8-OHdG), and xanthine oxidase (XOD) activity. In contrast, the AntioxyScore was determined through the catalase (CAT) and superoxide dismutase (SOD) activity, as well as the total antioxidant capacity (TAC). Patients with CAS displayed enhanced oxidative stress compared to control subjects, probably exceeding their antioxidant capacity. Interestingly, patients with CAS and T2DM displayed less oxidative stress, possibly due to the benefits of their pharmacological therapy (metformin). Thus, reducing oxidative stress or enhancing antioxidant capacity through specific therapies could be a good strategy to manage CAS, focusing on personalized medicine., Depto. de Farmacología y Toxicología, Fac. de Medicina, TRUE, pub

Published
2023

48. Global Oxidative Status Is Linked to Calcific Aortic Stenosis: The Differences Due to Diabetes Mellitus and the Effects of Metformin

Author

Corbacho-Alonso, Nerea, primary, Rodríguez-Sánchez, Elena, additional, Sastre-Oliva, Tamara, additional, Mercado-García, Elisa, additional, Perales-Sánchez, Ines, additional, Juarez-Alia, Cristina, additional, López-Almodovar, Luis F., additional, Padial, Luis R., additional, Tejerina, Teresa, additional, Mourino-Alvarez, Laura, additional, Ruiz-Hurtado, Gema, additional, and Barderas, María G., additional

Published
2023
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