An Overview of the Cardiorenal Protective Mechanisms of SGLT2 Inhibitors
Sodium-glucose co-transporter 2 (SGLT2) inhibitors block glucose reabsorption in the renal proximal tubule, an insulin-independent mechanism that plays a critical role in glycemic regulation in diabetes. In addition to their glucose-lowering effects, SGLT2 inhibitors prevent both renal damage and th...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/7/3651 |
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| author | Teresa Salvatore Raffaele Galiero Alfredo Caturano Luca Rinaldi Anna Di Martino Gaetana Albanese Jessica Di Salvo Raffaella Epifani Raffaele Marfella Giovanni Docimo Miriam Lettieri Celestino Sardu Ferdinando Carlo Sasso |
| author_facet | Teresa Salvatore Raffaele Galiero Alfredo Caturano Luca Rinaldi Anna Di Martino Gaetana Albanese Jessica Di Salvo Raffaella Epifani Raffaele Marfella Giovanni Docimo Miriam Lettieri Celestino Sardu Ferdinando Carlo Sasso |
| author_sort | Teresa Salvatore |
| collection | DOAJ |
| description | Sodium-glucose co-transporter 2 (SGLT2) inhibitors block glucose reabsorption in the renal proximal tubule, an insulin-independent mechanism that plays a critical role in glycemic regulation in diabetes. In addition to their glucose-lowering effects, SGLT2 inhibitors prevent both renal damage and the onset of chronic kidney disease and cardiovascular events, in particular heart failure with both reduced and preserved ejection fraction. These unexpected benefits prompted changes in treatment guidelines and scientific interest in the underlying mechanisms. Aside from the target effects of SGLT2 inhibition, a wide spectrum of beneficial actions is described for the kidney and the heart, even though the cardiac tissue does not express SGLT2 channels. Correction of cardiorenal risk factors, metabolic adjustments ameliorating myocardial substrate utilization, and optimization of ventricular loading conditions through effects on diuresis, natriuresis, and vascular function appear to be the main underlying mechanisms for the observed cardiorenal protection. Additional clinical advantages associated with using SGLT2 inhibitors are antifibrotic effects due to correction of inflammation and oxidative stress, modulation of mitochondrial function, and autophagy. Much research is required to understand the numerous and complex pathways involved in SGLT2 inhibition. This review summarizes the current known mechanisms of SGLT2-mediated cardiorenal protection. |
| first_indexed | 2024-03-09T11:47:22Z |
| format | Article |
| id | doaj.art-4a15bbbe2be14fbf9d4735eb97aac0a7 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T11:47:22Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-4a15bbbe2be14fbf9d4735eb97aac0a72023-11-30T23:20:03ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-03-01237365110.3390/ijms23073651An Overview of the Cardiorenal Protective Mechanisms of SGLT2 InhibitorsTeresa Salvatore0Raffaele Galiero1Alfredo Caturano2Luca Rinaldi3Anna Di Martino4Gaetana Albanese5Jessica Di Salvo6Raffaella Epifani7Raffaele Marfella8Giovanni Docimo9Miriam Lettieri10Celestino Sardu11Ferdinando Carlo Sasso12Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via De Crecchio 7, 80138 Naples, ItalyDepartment of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, 80138 Naples, ItalyDepartment of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, 80138 Naples, ItalyDepartment of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, 80138 Naples, ItalyDepartment of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, 80138 Naples, ItalyDepartment of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, 80138 Naples, ItalyDepartment of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, 80138 Naples, ItalyDepartment of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, 80138 Naples, ItalyDepartment of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, 80138 Naples, ItalyDepartment of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, 80138 Naples, ItalyDivision of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, 3.31 Core Technology Facility, 46 Grafton Street, Manchester M13 9NT, UKDepartment of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, 80138 Naples, ItalyDepartment of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Luigi Miraglia 2, 80138 Naples, ItalySodium-glucose co-transporter 2 (SGLT2) inhibitors block glucose reabsorption in the renal proximal tubule, an insulin-independent mechanism that plays a critical role in glycemic regulation in diabetes. In addition to their glucose-lowering effects, SGLT2 inhibitors prevent both renal damage and the onset of chronic kidney disease and cardiovascular events, in particular heart failure with both reduced and preserved ejection fraction. These unexpected benefits prompted changes in treatment guidelines and scientific interest in the underlying mechanisms. Aside from the target effects of SGLT2 inhibition, a wide spectrum of beneficial actions is described for the kidney and the heart, even though the cardiac tissue does not express SGLT2 channels. Correction of cardiorenal risk factors, metabolic adjustments ameliorating myocardial substrate utilization, and optimization of ventricular loading conditions through effects on diuresis, natriuresis, and vascular function appear to be the main underlying mechanisms for the observed cardiorenal protection. Additional clinical advantages associated with using SGLT2 inhibitors are antifibrotic effects due to correction of inflammation and oxidative stress, modulation of mitochondrial function, and autophagy. Much research is required to understand the numerous and complex pathways involved in SGLT2 inhibition. This review summarizes the current known mechanisms of SGLT2-mediated cardiorenal protection.https://www.mdpi.com/1422-0067/23/7/3651type 2 diabetes mellitusgliflozinscardiovascular diseasediabetic kidney diseasecardiorenal protectioncardiorenal syndrome |
| spellingShingle | Teresa Salvatore Raffaele Galiero Alfredo Caturano Luca Rinaldi Anna Di Martino Gaetana Albanese Jessica Di Salvo Raffaella Epifani Raffaele Marfella Giovanni Docimo Miriam Lettieri Celestino Sardu Ferdinando Carlo Sasso An Overview of the Cardiorenal Protective Mechanisms of SGLT2 Inhibitors International Journal of Molecular Sciences type 2 diabetes mellitus gliflozins cardiovascular disease diabetic kidney disease cardiorenal protection cardiorenal syndrome |
| title | An Overview of the Cardiorenal Protective Mechanisms of SGLT2 Inhibitors |
| title_full | An Overview of the Cardiorenal Protective Mechanisms of SGLT2 Inhibitors |
| title_fullStr | An Overview of the Cardiorenal Protective Mechanisms of SGLT2 Inhibitors |
| title_full_unstemmed | An Overview of the Cardiorenal Protective Mechanisms of SGLT2 Inhibitors |
| title_short | An Overview of the Cardiorenal Protective Mechanisms of SGLT2 Inhibitors |
| title_sort | overview of the cardiorenal protective mechanisms of sglt2 inhibitors |
| topic | type 2 diabetes mellitus gliflozins cardiovascular disease diabetic kidney disease cardiorenal protection cardiorenal syndrome |
| url | https://www.mdpi.com/1422-0067/23/7/3651 |
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