Hallmarks of cardiovascular ageing

Nature Reviews Cardiology, Год журнала: 2023, Номер 20(11), С. 754 - 777

Опубликована: Май 16, 2023

Язык: Английский

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EMPA-KIDNEY: expanding the range of kidney protection by SGLT2 inhibitors

Clinical Kidney Journal, Год журнала: 2023, Номер 16(8), С. 1187 - 1198

Опубликована: Июнь 16, 2023

In the EMPA-KIDNEY (The Study of Heart and Kidney Protection With Empagliflozin) trial, empagliflozin reduced cardiorenal outcomes by 28% (hazard ratio 0.72; 95% confidence interval 0.64-0.82;

Язык: Английский

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Critical Analysis of the Effects of SGLT2 Inhibitors on Renal Tubular Sodium, Water and Chloride Homeostasis and Their Role in Influencing Heart Failure Outcomes

Circulation, Год журнала: 2023, Номер 148(4), С. 354 - 372

Опубликована: Июль 24, 2023

SGLT2 (sodium-glucose cotransporter 2) inhibitors interfere with the reabsorption of glucose and sodium in early proximal renal tubule, but magnitude duration any ensuing natriuretic or diuretic effect are result an interplay between degree upregulation sodium-hydrogen exchanger 3, extent to which downstream compensatory tubular mechanisms activated, (potentially) volume set point individual patients. A comprehensive review synthesis available studies reveals several response patterns substantial variation across clinical settings. However, common observation is absence a large acute chronic diuresis natriuresis these agents, either when given alone combined other diuretics. This limited results from fact that compensation drugs rapid nearly complete within few days weeks, preventing progressive losses. Nevertheless, finding fractional excretion lithium (the latter being marker reabsorption) persists during long-term treatment indicates pharmacological tolerance effects at level tubule does not meaningfully occur. persistent can be hypothesized produce durable improvement internal for homeostasis, may become clinically important times fluid expansion. it difficult know whether treatment-related change actually occurs contributes reduce risk major heart failure events. exert cardioprotective by direct on cardiomyocytes independent presence binding actions tubule. changes mediated might potentially act cooperatively favorable molecular cellular mediate their benefits development course failure.

Язык: Английский

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Hyperuricemia and Gout Reduction by SGLT2 Inhibitors in Diabetes and Heart Failure

Journal of the American College of Cardiology, Год журнала: 2024, Номер 83(2), С. 371 - 381

Опубликована: Янв. 1, 2024

Gout is characterized by increased production of purines (through the pentose phosphate pathway), which coupled with reduced renal or intestinal excretion urate. Concurrent upregulation nutrient surplus signaling (mammalian target rapamycin and hypoxia-inducible factor-1a) downregulation deprivation (sirtuin-1 adenosine monophosphate–activated protein kinase) redirects glucose toward anabolic pathways (rather than triphosphate production), thus promoting heightened oxidative stress cardiomyocyte proximal tubular dysfunction, leading to cardiomyopathy kidney disease. Hyperuricemia a marker driver) these cellular stresses. By inducing state starvation mimicry in surplus, sodium-glucose cotransporter-2 inhibitors decrease flux through pathway (thereby attenuating purine urate synthesis) while excretion. These convergent actions exert meaningful effect lower serum uric acid ≈0.6 1.5 mg/dL reduce risk gout 30% 50% large-scale clinical trials.

Язык: Английский

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Sodium–glucose cotransporter 2 inhibitors for transthyretin amyloid cardiomyopathy: Analyses of short‐term efficacy and safety

European Journal of Heart Failure, Год журнала: 2024, Номер 26(4), С. 938 - 947

Опубликована: Март 15, 2024

Язык: Английский

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Caloric restriction and its mimetics in heart failure with preserved ejection fraction: mechanisms and therapeutic potential

Cardiovascular Diabetology, Год журнала: 2025, Номер 24(1)

Опубликована: Янв. 18, 2025

Язык: Английский

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Mechanisms of enhanced renal and hepatic erythropoietin synthesis by sodium–glucose cotransporter 2 inhibitors

European Heart Journal, Год журнала: 2023, Номер 44(48), С. 5027 - 5035

Опубликована: Апрель 22, 2023

Abstract Sodium–glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of major heart failure events, an action that is statistically linked to enhanced erythropoiesis, suggesting stimulation erythropoietin and cardioprotection are related a shared mechanism. Four hypotheses have been proposed explain how these drugs increase production: (i) renal cortical reoxygenation with rejuvenation erythropoietin-producing cells; (ii) counterregulatory distal sodium reabsorption leading increased tubular workload oxygen consumption, thus, localized hypoxia; (iii) iron mobilization as stimulus hypoxia-inducible factor-2α (HIF-2α)-mediated synthesis; (iv) direct HIF-2α activation gene transcription due sirtuin-1 (SIRT1) signaling. The first two assume source interstitial fibroblast-like cells in deep cortex. However, SGLT2 do not alter regional tissue tension non-diabetic kidney, synthesis markedly impaired patients anemia chronic kidney disease, yet, produce unattenuated erythrocytic response patients. This observation raises possibility liver contributes production during inhibition. Hypoxia-inducible coexpressed only but also hepatocytes; site when maintained for prolonged periods. ability improve by derepressing hepcidin ferritin would be expected cytosolic ferrous iron, which might stimulate expression both through regulatory protein 1. Alternatively, established enhance SIRT1 mechanism drugs. In hepatic cell lines, can directly activate deacetylation, additionally, effect SIRT liver, peroxisome proliferator-activated receptor-γ coactivator-1α binds nuclear factor 4 promote erythropoietin. Since up-regulation exerts cytoprotective effects on stimulates erythropoietin, it well-positioned represent links erythropoiesis

Язык: Английский

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Ginsenoside Rb1 promotes the activation of PPARα pathway via inhibiting FADD to ameliorate heart failure

European Journal of Pharmacology, Год журнала: 2023, Номер 947, С. 175676 - 175676

Опубликована: Март 30, 2023

Язык: Английский

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Pathomechanisms of Diabetic Kidney Disease

Journal of Clinical Medicine, Год журнала: 2023, Номер 12(23), С. 7349 - 7349

Опубликована: Ноя. 27, 2023

The worldwide occurrence of diabetic kidney disease (DKD) is swiftly rising, primarily attributed to the growing population individuals affected by type 2 diabetes. This surge has been transformed into a substantial global concern, placing additional strain on healthcare systems already grappling with significant demands. pathogenesis DKD intricate, originating hyperglycemia, which triggers various mechanisms and pathways: metabolic, hemodynamic, inflammatory, fibrotic ultimately lead renal damage. Within each pathway, several mediators contribute development structural functional changes. Some these mediators, such as inflammatory cytokines, reactive oxygen species, transforming growth factor β are shared among different pathways, leading overlap interaction between them. While current treatment options for have shown advancement over previous strategies, their effectiveness remains somewhat constrained patients still experience residual risk progression. Therefore, comprehensive grasp molecular underlying onset progression imperative continued creation novel groundbreaking therapies this condition. In review, we discuss achievements in fundamental research, particular emphasis individual factors recent developments treatment.

Язык: Английский

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Sodium–glucose cotransporter‐2 inhibitors in heart failure: Potential decongestive mechanisms and current clinical studies

European Journal of Heart Failure, Год журнала: 2023, Номер 25(9), С. 1526 - 1536

Опубликована: Июль 21, 2023

Congestion is a key pathophysiological feature of heart failure (HF) syndrome that drives most the clinical manifestations acute HF and related with poor quality life outcomes. Therefore, safe effective decongestion an important therapeutic target in management despite use guideline-recommended loop diuretics, adequate not always achieved patients HF. Recently, sodium-glucose cotransporter-2 (SGLT-2) inhibitors have been shown to provide benefits across broad spectrum HF, including consistent reduction risk episodes. While exact mechanisms underlying these remain matter debate, growing body evidence suggests may be partly responsible, especially setting In this review, we discuss potential decongestive SGLT-2 inhibitors, such as osmotic diuresis, natriuresis, preservation glomerular filtration facilitation interstitial drainage, which can collectively translate into decongestion. Furthermore, comprehensive review up-to-date data inhibitor population.

Язык: Английский

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