Exogenous Ketones in Cardiovascular Disease and Diabetes: From Bench to Bedside DOI Open Access
Urna Kansakar, Crystal Nieves Garcia,

Gaetano Santulli

и другие.

Journal of Clinical Medicine, Год журнала: 2024, Номер 13(23), С. 7391 - 7391

Опубликована: Дек. 4, 2024

Ketone bodies are molecules produced from fatty acids in the liver that act as energy carriers to peripheral tissues when glucose levels low. Carbohydrate- and calorie-restricted diets, known increase of circulating ketone bodies, have attracted significant attention recent years due their potential health benefits several diseases. Specifically, increasing ketones through dietary modulation has been reported be beneficial for cardiovascular improve homeostasis insulin resistance. Interestingly, although excessive production may lead life-threatening ketoacidosis diabetic patients, mounting evidence suggests modest play adaptive roles pancreatic beta cells, exact mechanisms still unknown. Of note, Sodium-Glucose Transporter 2 (SGLT2) inhibitors shown beta-hydroxybutyrate (BHB), most abundant human body, which a pivotal role mediating some protective effects diabetes. This systematic review provides comprehensive overview scientific literature presents an analysis on pathophysiology cell function. The both preclinical clinical studies indicates exogenous cardiomyocytes making them intriguing candidates cardioprotective therapies preserve function patients with

Язык: Английский

Endothelial Protection by Sodium-Glucose Cotransporter 2 Inhibitors: A Literature Review of In Vitro and In Vivo Studies DOI Open Access

N Mylonas,

Panagiota Nikolaou, Paschalis Karakasis

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(13), С. 7274 - 7274

Опубликована: Июль 2, 2024

Endothelial dysfunction often precedes the development of cardiovascular diseases, including heart failure. The cardioprotective benefits sodium-glucose cotransporter 2 inhibitors (SGLT2is) could be explained by their favorable impact on endothelium. In this review, we summarize current knowledge direct in vitro effects SGLT2is endothelial cells, as well systematic observations preclinical models. Four putative mechanisms are explored: oxidative stress, nitric oxide (NO)-mediated pathways, inflammation, and cell survival proliferation. Both vivo studies suggest that share a class effect attenuating reactive oxygen species (ROS) enhancing NO bioavailability increasing synthase activity reducing scavenging ROS. Moreover, significantly suppress inflammation preventing expression adhesion receptors pro-inflammatory chemokines vivo, indicating another for protection. However, have not consistently shown regulation molecule SGLT2is. While improve under death-inducing stimuli, angiogenesis remains uncertain. Further experimental required to accurately determine interplay among these various complications, failure acute myocardial infarction.

Язык: Английский

Процитировано

17
Sodium-Glucose-Cotransporter-2 Inhibitor Therapy and Intermitted Fasting in Cardiorenal Syndrome: The Role of Glucose-Mediated Oxidative Stress DOI Open Access
Katrin Schröder

Journal of Clinical Medicine, Год журнала: 2025, Номер 14(3), С. 746 - 746

Опубликована: Янв. 24, 2025

Cardiorenal syndrome (CRS) is a complex clinical disorder characterized by the interplay between heart and kidney dysfunction. This condition exacerbated comorbidities such as diabetes mellitus, which contribute to glucose-mediated oxidative stress, further complicating management of CRS. The CRS has evolved with discovery sodium-glucose-cotransporter-2 (SGLT2) inhibitors, have been established effective agents in reducing hyperglycemia demonstrated cardiorenal protective effects. Concurrently, intermittent fasting gained attention an intervention without pharmacological treatment for its metabolic benefits, including improved glucose metabolism insulin regulation sensitivity, both potential reduction stress. review provides summary current findings on roles SGLT2 inhibitors managing CRS, particular focus We evaluate mechanisms these interventions exert their effects, identify gaps research, offer recommendations future studies. While demonstrate more research needed elucidate long-term efficacy, safety, synergistic

Язык: Английский

Процитировано

1
A review regarding the article ‘Targeting inflammatory signaling pathways with SGLT2 inhibitors: Insights into cardiovascular health and cardiac cell improvement’ DOI

Xiaoqin He,

Dou Yuan

Current Problems in Cardiology, Год журнала: 2024, Номер 49(6), С. 102563 - 102563

Опубликована: Апрель 8, 2024

Язык: Английский

Процитировано

4
Dapagliflozin mitigates cellular stress and inflammation through PI3K/AKT pathway modulation in cardiomyocytes, aortic endothelial cells, and stem cell-derived β cells DOI Creative Commons

Fatmah R. Alsereidi,

Zenith Khashim,

Hezlin Marzook

и другие.

Cardiovascular Diabetology, Год журнала: 2024, Номер 23(1)

Опубликована: Окт. 29, 2024

Dapagliflozin (DAPA), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, is well-recognized for its therapeutic benefits in type diabetes (T2D) and cardiovascular diseases. In this comprehensive vitro study, we investigated DAPA's effects on cardiomyocytes, aortic endothelial cells (AECs), stem cell-derived beta (SC-β), focusing impact hypertrophy, inflammation, cellular stress. Our results demonstrate that DAPA effectively attenuates isoproterenol (ISO)-induced hypertrophy reducing cell size improving structure. Mechanistically, mitigates reactive oxygen species (ROS) production inflammation by activating the AKT pathway, which influences downstream markers of fibrosis, inflammation. Additionally, modulation SGLT2, Na+/H + exchanger 1 (NHE1), glucose transporter (GLUT 1) highlights critical role maintaining ion balance metabolism, providing insights into cardioprotective mechanisms. exhibited notable anti-inflammatory properties restoring phosphoinositide 3-kinase (PI3K) expression, enhancing mitogen-activated protein kinase (MAPK) activation, downregulating inflammatory cytokines at both gene levels. Furthermore, alleviated tumor necrosis factor (TNFα)-induced stress responses while nitric oxide synthase (eNOS) suggesting potential to preserve vascular function improve health. Investigating SC-β cells, found enhances insulin functionality without altering identity, indicating management. also upregulated MAFA, PI3K, NRF2 positively influencing β-cell response. it attenuated NLRP3 activation reduced NHE1 glucose-regulated GRP78 offering novel stress-modulating effects. Overall, our findings elucidate multifaceted across various models, emphasizing mitigating through pathway other signaling cascades. These mechanisms may not only contribute enhanced cardiac but underscore address metabolic dysregulation T2D.

Язык: Английский

Процитировано

4
Inflammation in Heart Failure: Mechanisms and Therapeutic Strategies DOI Creative Commons
Yu Jiang,

Guoxiang Zhou,

Yongzheng Guo

и другие.

Cardiovascular Innovations and Applications, Год журнала: 2025, Номер 9(1)

Опубликована: Янв. 1, 2025

Cardiovascular disease remains a leading cause of death and disability worldwide. Heart failure (HF) is the end stage various cardiovascular diseases. Despite recent advancements in understanding HF pathogenesis treatment, prognosis patients with poor. Inflammation key player development HF, its role has been extensively studied. associated elevated risk adverse prognosis. Targeting cardiac inflammation suggested as promising treatment strategy for HF. However, almost all clinical trials on anti-inflammatory have not indicated improved outcomes, some reported deterioration condition, possibly because limited specific The summary inflammatory mechanisms contributing to different types, current anti-inflammation therapies results could provide new perspectives targeting through effective therapeutic strategies.

Язык: Английский

Процитировано

0
COMPUTATIONAL QSAR-BASED MACHINE LEARNING APPROACH FOR PREDICTING ACTIVITY OF SGLT2 INHIBITORS USING THE KNIME PLATFORM DOI Open Access

Adha Dastu Illahi,

Gatot Fatwanto Hertono,

Arry Yanuar

и другие.

International Journal of Applied Pharmaceutics, Год журнала: 2025, Номер unknown, С. 328 - 333

Опубликована: Янв. 7, 2025

Objective: This study aims to identify optimal predictive models and key molecular fragments by preparing a dataset using machine learning techniques within the Konstanz Information Miner (KNIME) platform. Methods: The human Sodium-glucose Cotransporter 2 (SGLT2) target was obtained from ChEMBL database refined removing salts, incomplete/incorrect data, duplicates. data classified into active inactive compounds, fingerprints descriptors were calculated. Christian Borgelt's Molecular Substructure (MoSS) employed frequent fragments. Following partitioning, various ‘classification’ ‘regression’ (ML) based Quantitative Structure-Activity Relationship (QSAR) developed evaluated different techniques, including sensitivity Mean Squared Error (MSE). Results: In QSAR classification, Support Vector Machine (SVM) model demonstrated best performance with an accuracy of 81.66%, while in Regression, Extreme Gradient Boosting (XGB) exhibited coefficient determination (R2) Absolute (MAE) values 0.69 0.47 respectively. identification Fragments highlighted common characteristics SGLT2 inhibitors. Conclusion: results developing these indicate that methods can be effectively used predict inhibitors virtually, thereby expediting drug discovery process.

Язык: Английский

Процитировано

0
Sodium-Glucose Cotransporter-2 Inhibitor Improves Renal Injury by Regulating the Redox Profile, Inflammatory Parameters, and Pyroptosis in an Experimental Model of Diabetic Kidney Disease DOI Creative Commons
Paulo André Bispo Machado Júnior, André Domingos Lass,

Julia de Bortolo

и другие.

ACS Pharmacology & Translational Science, Год журнала: 2025, Номер unknown

Опубликована: Апрель 16, 2025

Язык: Английский

Процитировано

0
Stress Granules in Atherosclerosis: Insights and Therapeutic Opportunities DOI

Sahar Naseem,

Lijuan Sun,

Juhui Qiu

и другие.

Current Problems in Cardiology, Год журнала: 2024, Номер 49(10), С. 102760 - 102760

Опубликована: Июль 24, 2024

Язык: Английский

Процитировано

2
Novel Compounds as NLRP3 Inhibitors for Treating Cardiovascular Diseases DOI
Ram W. Sabnis

ACS Medicinal Chemistry Letters, Год журнала: 2024, Номер 15(8), С. 1184 - 1185

Опубликована: Июль 11, 2024

Provided herein are novel compounds as NLRP3 inhibitors, pharmaceutical compositions, use of such in treating cardiovascular diseases, and processes for preparing compounds.

Язык: Английский

Процитировано

0
The role of NF-κB in diabetic cardiomyopathy DOI Creative Commons

Huang-Jun Liu,

Le-Kun Gui, Wei Han

и другие.

All Life, Год журнала: 2024, Номер 17(1)

Опубликована: Сен. 5, 2024

Язык: Английский

Процитировано

0