SGLT2 Inhibition via Empagliflozin Improves Endothelial Function and Reduces Mitochondrial Oxidative Stress: Insights From Frail Hypertensive and Diabetic Patients

Hypertension, Год журнала: 2022, Номер 79(8), С. 1633 - 1643

Опубликована: Июль 13, 2022

Frailty is a multidimensional condition often diagnosed in older adults with hypertension and diabetes, both these conditions are associated endothelial dysfunction oxidative stress. We investigated the functional role of SGLT2 (sodium glucose cotransporter 2) inhibitor empagliflozin frail diabetic hypertensive adults.

Язык: Английский

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COVID-19 Causes Ferroptosis and Oxidative Stress in Human Endothelial Cells

Antioxidants, Год журнала: 2023, Номер 12(2), С. 326 - 326

Опубликована: Янв. 31, 2023

Oxidative stress and endothelial dysfunction have been shown to play crucial roles in the pathophysiology of COVID-19 (coronavirus disease 2019). On these grounds, we sought investigate impact on lipid peroxidation ferroptosis human cells. We hypothesized that oxidative induced by cells could be linked outcome. Thus, collected serum from patients hospital admission, incubated sera with cells, comparing effects generation reactive oxygen species (ROS) between who survived did not survive. found non-survivors significantly increased peroxidation. Moreover, markedly regulated expression levels main markers ferroptosis, including GPX4, SLC7A11, FTH1, SAT1, a response was rescued silencing TNFR1 Taken together, our data indicate survive triggers

Язык: Английский

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Sodium-glucose cotransporter-2 inhibitors and their potential role in dementia onset and cognitive function in patients with diabetes mellitus: a systematic review and meta-analysis

Frontiers in Neuroendocrinology, Год журнала: 2024, Номер 73, С. 101131 - 101131

Опубликована: Фев. 16, 2024

This systematic review and meta-analysis aimed to determine the association between use of sodium-glucose cotransporter 2 (SGLT-2) inhibitors dementia onset as well cognitive function in patients with diabetes mellitus. We comprehensively searched MEDLINE, Embase, CENTRAL databases select relevant studies published up August 2023. The SGLT-2 significantly lowers risk compared SGLT-2i non-users (Hazard ratio: 0.68, 95 % CI: 0.50-0.92). Furthermore, our findings indicated a positive effect inhibitor on score improvement, demonstrated by standardized mean difference 0.88 (95 0.32-1.44), particularly among populations mild impairment or dementia. indicate potential role reducing These underscore need for well-controlled large clinical trials future research this field.

Язык: Английский

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Functional and Clinical Importance of SGLT2-inhibitors in Frailty: From the Kidney to the Heart

Hypertension, Год журнала: 2023, Номер 80(9), С. 1800 - 1809

Опубликована: Июль 5, 2023

SGLT2 (sodium-glucose cotransporter 2) enables glucose and sodium reabsorption in the kidney. SGLT2-inhibitors (also known as gliflozins, which include canagliflozin, dapagliflozin, empagliflozin, ertugliflozin) act by increasing glycosuria, thereby reducing glycemia. These drugs are critical to reach keep glycemic control, a crucial feature, especially patients with comorbidities, like frail individuals. Several studies evaluated effects of different settings beyond diabetes, revealing that they actually pleiotropic drugs. We recently evidenced favorable SGLT2-inhibition on physical cognitive impairment older adults diabetes hypertension. In present overview, we summarize latest clinical preclinical exploring main kidney heart, emphasizing their potential beneficial actions frailty.

Язык: Английский

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Repurposing SGLT-2 Inhibitors to Target Aging: Available Evidence and Molecular Mechanisms

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(20), С. 12325 - 12325

Опубликована: Окт. 14, 2022

Caloric restriction promotes longevity in multiple animal models. Compounds modulating nutrient-sensing pathways have been suggested to reproduce part of the beneficial effect caloric on aging. However, none commonly studied mimetics actually produce a decrease calories. Sodium-glucose cotransporter 2 inhibitors (SGLT2-i) are class drugs which lower glucose by promoting its elimination through urine, thus inducing net loss This metabolic shift at systemic level, fostering ketones and fatty acids utilization as glucose-alternative substrates, is accompanied modulation major held drive aging, e.g., mTOR inflammasome, overall resembling features restriction. In addition, preliminary experimental data suggest that SGLT-2i might also intrinsic activities independent their effects, such inhibition cellular senescence. Consistently, evidence from both preclinical clinical studies marked ability ameliorate low-grade inflammation humans, relevant driver aging referred inflammaging. Considering amount trials, observational studies, meta-analyses suggesting tangible age-related outcomes, cardiovascular diseases, heart failure, kidney disease, all-cause mortality patients without diabetes, here we propose framework where least benefit provided mediated blunt drivers To support this postulate, synthesize available relative on: 1- models healthspan lifespan; 2- selected molecular pillars models; 3- biomarkers especially inflammaging humans; 4- COVID-19-related outcomes. The burden prompt design testing potential employment anti-aging drugs.

Язык: Английский

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Mechanisms of benefits of sodium-glucose cotransporter 2 inhibitors in heart failure with preserved ejection fraction

European Heart Journal, Год журнала: 2023, Номер 44(37), С. 3640 - 3651

Опубликована: Июнь 13, 2023

For decades, heart failure with preserved ejection fraction (HFpEF) proved an elusive entity to treat. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have recently been shown reduce the composite of hospitalization or cardiovascular death in patients HFpEF landmark DELIVER and EMPEROR-Preserved trials. While improvements blood sugar, pressure, attenuation kidney disease progression all may play some role, preclinical translational research identified additional mechanisms these agents. The SGLT2 intriguingly induce a nutrient-deprivation hypoxic-like transcriptional paradigm, increased ketosis, erythropoietin, autophagic flux addition altering iron homeostasis, which contribute improved cardiac energetics function. These agents also epicardial adipose tissue alter adipokine signalling, role reductions inflammation oxidative stress observed inhibition. Emerging evidence indicates that drugs impact cardiomyocyte ionic homeostasis although whether this is through indirect via direct, off-target effects on other ion channels has yet be clearly characterized. Finally, myofilament stiffness as well extracellular matrix remodelling/fibrosis heart, improving diastolic established themselves robust, disease-modifying therapies recent trial results are incorporated into clinical guidelines, will likely become foundational therapy HFpEF.

Язык: Английский

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miR-181c targets Parkin and SMAD7 in human cardiac fibroblasts: Validation of differential microRNA expression in patients with diabetes and heart failure with preserved ejection fraction

Mechanisms of Ageing and Development, Год журнала: 2023, Номер 212, С. 111818 - 111818

Опубликована: Апрель 27, 2023

Язык: Английский

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Effectiveness and safety of the combination of sodium–glucose transport protein 2 inhibitors and glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of observational studies

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

Опубликована: Март 18, 2024

Abstract Background Randomized controlled trials and real-world studies suggest that combination therapy with sodium–glucose transport protein 2 inhibitors (SGLT2is) glucagon-like peptide-1 receptor agonists (GLP-1RAs) is associated improvement in fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), systolic blood pressure (SBP), body mass index (BMI), total cholesterol levels. However, a systematic review of available evidence may facilitate clinical decision-making the scenario. This meta-analysis assessed safety effectiveness combinations SGLT2is + GLP-1RAs focus on their cardioprotective effects along glucose-lowering ability patients type diabetes mellitus (T2DM) setting. Methods Electronic searches were performed PubMed/MEDLINE, PROQuest, Scopus, CINAHL, Google Scholar databases. Qualitative analyses meta-analyses using Joanna Briggs Institute SUMARI software package Review Manager v5.4, respectively. Results The initial database search yielded 1445 articles; these, 13 included this study. indicated significantly lower all-cause mortality when compared individual therapies (odds ratio [95% confidence interval [CI] 0.49 [0.41, 0.60]; p < 0.00001). Significant reductions BMI (− 1.71 [− 2.74, − 0.67]; = 0.001), SBP 6.35 10.17, 2.53]; HbA1c levels 1.48 1.75, 1.21]; 0.00001), FPG 2.27 2.78, 1.76]; 0.00001) simultaneous administration combination. Changes differences between sequential for outcome not significant. Conclusion based data suggests favorable improvements cardiovascular, renal, glycemic measurements. findings drive call-to–action to incorporate early simultaneously managing T2DM achieve potential cardiovascular benefits renal protection. Graphical

Язык: Английский

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Endothelial Dysfunction in Obesity and Therapeutic Targets

Advances in experimental medicine and biology, Год журнала: 2024, Номер unknown, С. 489 - 538

Опубликована: Янв. 1, 2024

Язык: Английский

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Non-coding RNAs in the pathophysiology of heart failure with preserved ejection fraction

Frontiers in Cardiovascular Medicine, Год журнала: 2024, Номер 10

Опубликована: Янв. 8, 2024

Heart failure with preserved ejection fraction (HFpEF) is the largest unmet clinical need in cardiovascular medicine. Despite decades of research, treatment option for HFpEF still limited, indicating our ongoing incomplete understanding on underlying molecular mechanisms. Non-coding RNAs, comprising microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular (circRNAs), are non-protein coding RNA transcripts, which implicated various diseases. However, their role pathogenesis unknown. Here, we discuss miRNAs, lncRNAs circRNAs that involved pathophysiology HFpEF, namely microvascular dysfunction, inflammation, diastolic dysfunction cardiac fibrosis. We interrogated evidence dissected mechanisms ncRNAs by looking at relevant vivo vitro models mimic co-morbidities patients HFpEF. Finally, potential as biomarkers novel therapeutic targets future treatment.

Язык: Английский

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