Single-cell multi-omics analysis reveals the mechanism of action of a novel antioxidant polyphenol nanoparticle loaded with STAT3 agonist in mediating cardiomyocyte ferroptosis to ameliorate age-related heart failure DOI Creative Commons
Haoyuan Zheng, Yuan Tian, Dongyu Li

et al.

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 29, 2025

Heart failure (HF) is a prevalent and critical cardiac condition that leads to profound structural functional changes in the heart. Although traditional treatments have shown partial efficacy, long-term outcomes remain suboptimal. Emerging research has highlighted pivotal role of oxidative stress ferroptosis HF progression. This study investigates new therapeutic approach utilizing antioxidant polyphenol nanoparticles loaded with STAT3 agonist (PN@Col) target these pathways improve age-related HF. Key cells genes contributing progression were identified via analysis GEO database, single-cell RNA sequencing (scRNA-seq) AUCell used evaluate differential gene expression. The was as essential, its functionality further validated vitro through cell experiments, confirming impact on cardiomyocytes (CMs) Following development PN@Col, experiments showed PN@Col effectively reduced CMs. In vivo studies elderly mice demonstrated significant improvements function following treatment. offers promising by mitigating cardiomyocytes. These findings provide solid scientific foundation for potential novel treatment strategy HF, supporting exploration toward clinical application.

Language: Английский

The Aging Heart in Focus: The Advanced Understanding of Heart Failure with Preserved Ejection Fraction DOI

Zhe-Wei Zhang,

Yibin Wang, Xiangqi Chen

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 101, P. 102542 - 102542

Published: Oct. 12, 2024

Language: Английский

Citations

5
Cardiovascular aging: spotlight on mitochondria DOI
Md Akkas Ali, Rachel A. Gioscia‐Ryan, Dongli Yang

et al.

AJP Heart and Circulatory Physiology, Journal Year: 2023, Volume and Issue: 326(2), P. H317 - H333

Published: Dec. 1, 2023

Mitochondria are cellular organelles critical for ATP production and particularly relevant to cardiovascular diseases including heart failure, atherosclerosis, ischemia-reperfusion injury, cardiomyopathies. With advancing age, even in the absence of clinical disease, mitochondrial homeostasis becomes disrupted (e.g., redox balance, DNA damage, oxidative metabolism, quality control). Mitochondrial dysregulation leads accumulation damaged dysfunctional mitochondria, producing excessive reactive oxygen species perpetuating dysfunction. In addition, DNA, cardiolipin,

Language: Английский

Citations

12
Emerging Pathophysiological Roles of Ketone Bodies DOI

Hiroaki Tsuruta,

Kosuke Yamahara,

Mako Yasuda‐Yamahara

et al.

Physiology, Journal Year: 2024, Volume and Issue: 39(3), P. 167 - 177

Published: Jan. 23, 2024

The discovery of insulin approximately a century ago greatly improved the management diabetes, including many its life-threatening acute complications like ketoacidosis. This breakthrough saved lives and extended healthy lifespan patients with diabetes. However, there is still negative perception ketone bodies stemming from Originally, were thought as vital source energy during fasting exercise. Furthermore, in recent years, research on calorie restriction potential impact extending lifespans, well studies bodies, have gradually led to reevaluation significance promoting longevity. Thus, this review, we discuss emerging hidden roles various organs, heart, kidneys, skeletal muscles, brain, their malignancies lifespan.

Language: Английский

Citations

4
Progenitor Cell Function and Cardiovascular Remodelling Induced by SGLT2 Inhibitors DOI Creative Commons
Theodora M. Stougiannou, Konstantinos Christodoulou, Theocharis Koufakis

et al.

Frontiers in Bioscience-Landmark, Journal Year: 2024, Volume and Issue: 29(4), P. 145 - 145

Published: April 9, 2024

Sodium-glucose cotransporters 2 (SGLT2) are high-capacity, low-affinity transporters, expressed mainly in the early portion of proximal renal tube, mediating up to 90% glucose uptake, while SGLT1 receptors found small intestine, facilitating absorption. SGLT2 inhibitors (SGLT2i) originally emerged as agents for treatment type diabetes mellitus; however, they soon demonstrated remarkable cardio- and renoprotective actions that led their licensed use heart failure chronic kidney disease, regardless diabetic status. Cardiovascular remodelling represents an umbrella term encompasses changes occur cardiovascular system, from molecular cellular level, tissue organs after local injury, stress, or pressure. SGLT modulation has been shown positively affect many these observed during pathological remodelling. Among different pathophysiological mechanisms contribute adverse remodelling, various stem progenitor cells have be involved, through alterations number function. Recent studies examined effects SGLT2i on cell populations more specifically endothelial (EPCs). Although some no significant effect, others showed can modulate morphology function EPCs. These preliminary observations effect EPCs may responsible beneficial gliflozins and, by extension, disease. The purpose this narrative review is critically discuss recent evidence cardioprotective SGLT2is, context cardiac

Language: Английский

Citations

4
Circulating beta‐hydroxybutyrate levels in advanced heart failure with reduced ejection fraction: Determinants and prognostic impact DOI
Luca Monzo, J. Kovář, Barry A. Borlaug

et al.

European Journal of Heart Failure, Journal Year: 2024, Volume and Issue: unknown

Published: June 10, 2024

Language: Английский

Citations

4
Advances in the Insulin–Heart Axis: Current Therapies and Future Directions DOI Open Access
Alfredo Caturano,

Erica Vetrano,

Raffaele Galiero

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(18), P. 10173 - 10173

Published: Sept. 22, 2024

The insulin–heart axis plays a pivotal role in the pathophysiology of cardiovascular disease (CVD) insulin-resistant states, including type 2 diabetes mellitus. Insulin resistance disrupts glucose and lipid metabolism, leading to systemic inflammation, oxidative stress, atherogenesis, which contribute heart failure (HF) other CVDs. This review was conducted by systematically searching PubMed, Scopus, Web Science databases for peer-reviewed studies published past decade, focusing on therapeutic interventions targeting axis. Studies were selected based their relevance insulin resistance, outcomes, efficacy pharmacologic treatments. Key findings from highlight lifestyle modifications, such as dietary changes physical activity, remain cornerstone managing improving outcomes. Moreover, interventions, metformin, sodium–glucose cotransporter inhibitors, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 have shown reducing risk addressing metabolic dysfunction, endothelial function. Furthermore, emerging treatments, angiotensin receptor–neprilysin mechanical like ventricular assist devices offer new avenues HF patients. potential these therapies improve left ejection fraction reverse pathological cardiac remodeling highlights importance early intervention. However, challenges optimizing treatment regimens understanding long-term effects agents. Future research should focus personalized approaches that integrate effectively target mitigate burden complications populations.

Language: Английский

Citations

4
SGLT2 inhibition alters substrate utilization and mitochondrial redox in healthy and failing rat hearts DOI Creative Commons
Leigh Goedeke, Yina Ma, Rafael Calais Gaspar

et al.

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(24)

Published: Dec. 15, 2024

Previous studies highlight the potential for sodium-glucose cotransporter type 2 (SGLT2) inhibitors (SGLT2i) to exert cardioprotective effects in heart failure by increasing plasma ketones and shifting myocardial fuel utilization toward ketone oxidation. However, SGLT2i have multiple vivo differential impact of treatment supplementation on cardiac metabolism remains unclear. Here, using gas chromatography-mass spectrometry (GC-MS) liquid chromatography-tandem mass (LC-MS/MS) methodology combined with infusions [13C6]glucose or [13C4]βOHB, we demonstrate that acute SGLT2 inhibition dapagliflozin shifts relative rates mitochondrial oxidation, decreasing pyruvate oxidation little effect fatty acid awake rats. Shifts persisted when glucose levels were maintained. In contrast, βOHB infusion similarly augmented but markedly reduced did not alter uptake After inducing failure, increased decreased Dapagliflozin redox oxidative stress which was associated improvements left ventricular ejection fraction after 3 weeks treatment. Thus, pleiotropic systemic metabolism, are distinct from may contribute long-term benefits SGLT2i.

Language: Английский

Citations

4
Significance of Endothelial Dysfunction Amelioration for Sodium–Glucose Cotransporter 2 Inhibitor-Induced Improvements in Heart Failure and Chronic Kidney Disease in Diabetic Patients DOI Creative Commons
Hidekatsu Yanai,

Hiroki Adachi,

Mariko Hakoshima

et al.

Metabolites, Journal Year: 2023, Volume and Issue: 13(6), P. 736 - 736

Published: June 8, 2023

Beyond lowering plasma glucose levels, sodium–glucose cotransporter 2 inhibitors (SGLT2is) significantly reduce hospitalization for heart failure (HF) and retard the progression of chronic kidney disease (CKD) in patients with type diabetes. Endothelial dysfunction is not only involved development cardiovascular (CVD), but also associated CKD. In diabetes, hyperglycemia, insulin resistance, hyperinsulinemia dyslipidemia induce endothelial dysfunction. SGLT2is have been shown to improve dysfunction, as assessed by flow-mediated vasodilation, individuals at high risk CVD. Along an improvement oxidative stress, inflammation, mitochondrial glucotoxicity, such advanced signaling glycation end products, nitric oxide bioavailability. The improvements endothelium-derived factors may play important role preventing coronary artery disease, microvascular diabetic cardiomyopathy, which cause HF, a retarding suppression HF CKD achieved might largely induced their capacity vascular function.

Language: Английский

Citations

11
Metabolic Control of Cardiomyocyte Cell Cycle DOI Creative Commons
Ivan Menendez-Montes, Daniel J. Garry, Jianyi Zhang

et al.

Methodist DeBakey Cardiovascular Journal, Journal Year: 2023, Volume and Issue: 19(5), P. 26 - 36

Published: Jan. 1, 2023

Current therapies for heart failure aim to prevent the deleterious remodeling that occurs after MI injury, but currently no are available replace lost cardiomyocytes. Several organisms now being studied capable of regenerating their myocardium by proliferation existing In this review, we summarize main metabolic pathways mammalian and how modulation these through genetic pharmacological approaches influences cardiomyocyte regeneration.

Language: Английский

Citations

10
Therapeutic potential of ketone bodies on exercise intolerance in heart failure: looking beyond the heart DOI Creative Commons
Shubham Soni, Rachel J. Skow, Stephen J. Foulkes

et al.

Cardiovascular Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 18, 2025

Recent evidence suggests that ketone bodies have therapeutic potential in many cardiovascular diseases including heart failure (HF). Accordingly, this has led to multiple clinical trials use esters treat HF patients, which we term therapy. Ketone esters, specifically monoesters, are synthetic compounds which, when consumed, de-esterified into two β-hydroxybutyrate (βOHB) molecules and increase the circulating βOHB concentration. While studies primarily focused on cardiac benefits of therapy HF, ketones can numerous favorable effects other organs such as vasculature skeletal muscle. Importantly, vascular muscle dysfunction also heavily implicated reduced exercise tolerance, hallmark feature with (HFrEF) preserved (HFpEF) ejection fraction, suggesting some observed response may involve these non-cardiac pathways. Thus, review how be beneficial improving function identify various mechanisms important HF.

Language: Английский

Citations

0