Short-chain fatty acid metabolism and multiple effects on cardiovascular diseases

Ageing Research Reviews, Journal Year: 2022, Volume and Issue: 81, P. 101706 - 101706

Published: Aug. 4, 2022

Language: Английский

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Metabolic Flexibility of the Heart: The Role of Fatty Acid Metabolism in Health, Heart Failure, and Cardiometabolic Diseases

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 1211 - 1211

Published: Jan. 19, 2024

This comprehensive review explores the critical role of fatty acid (FA) metabolism in cardiac diseases, particularly heart failure (HF), and implications for therapeutic strategies. The heart’s reliance on ATP, primarily sourced from mitochondrial oxidative metabolism, underscores significance metabolic flexibility, with oxidation (FAO) being a dominant source. In HF, shifts occur an altered FA uptake FAO, impacting function contributing to disease progression. Conditions like obesity diabetes also lead disturbances, resulting cardiomyopathy marked by over-reliance dysfunction, lipotoxicity. Therapeutic approaches targeting diseases have evolved, focusing inhibiting or stimulating FAO optimize energetics. Strategies include using CPT1A inhibitors, PPARα agonists, enhancing biogenesis function. However, effectiveness varies, reflecting complexity remodeling HF. Hence, treatment strategies should be individualized, considering that energy is intricate tightly regulated. aim overall function, recognizing pivotal FAs need further research develop effective therapies, promising new improve

Language: Английский

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Resveratrol inhibits ferroptosis and decelerates heart failure progression via Sirt1/p53 pathway activation

Journal of Cellular and Molecular Medicine, Journal Year: 2023, Volume and Issue: 27(20), P. 3075 - 3089

Published: July 24, 2023

Resveratrol is an organic compound widely studied for its therapeutic uses. We investigated whether resveratrol exerts cardioprotective effects by inhibiting ferroptosis via the Sirt1/p53 pathway. A heart failure model was established aortic coarctation in Sirt1 knockout mice. The superoxide dismutase (SOD), glutathione (GSH) levels and mitochondrial morphology murine tissues were assessed at different time points to determine role of progression. cardiac function mice with evaluated determining brain natriuretic peptide (BNP) sST2 concentration conducting echocardiography. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) transfected p53 K382R mutant interference lentiviral vectors. Immunoprecipitation (IP) experiments performed investigate influences K382 acetylation SLC7A11 expression modulation. improved decelerated fibrosis progression failure. However, ability prevent treat lost after silencing Sirt1. reduced diminishing acetylation, reducing degradation SLC7A11, increasing GSH peroxidase 4 (GPX4) cells. In conclusion, activating pathway failure, decreased depletion inhibited ferroptosis, function.

Language: Английский

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Scalable Generation of Nanovesicles from Human-Induced Pluripotent Stem Cells for Cardiac Repair

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(22), P. 14334 - 14334

Published: Nov. 18, 2022

Extracellular vesicles (EVs) from stem cells have shown significant therapeutic potential to repair injured cardiac tissues and regulate pathological fibrosis. However, scalable generation of derived EVs for clinical utility remains a huge technical challenge. Here, we report rapid size-based extrusion strategy generate EV-like membranous nanovesicles (NVs) easily sourced human iPSCs in large quantities (yield 900× natural EVs). NVs isolated using density-gradient separation (buoyant density 1.13 g/mL) are spherical shape morphologically intact readily internalised by cardiomyocytes, primary fibroblasts, endothelial cells. captured the dynamic proteome parental include pluripotency markers (LIN28A, OCT4) regulators processes, including tissue (GJA1, HSP20/27/70, HMGB1), wound healing (FLNA, MYH9, ACTC1, ILK), stress response/translation initiation (eIF2S1/S2/S3/B4), hypoxia response (HMOX2, HSP90, GNB1), extracellular matrix organization (ITGA6, MFGE8, ITGB1). Functionally, significantly promoted tubule formation (angiogenesis) (p < 0.05) survival cardiomyocytes exposed low oxygen conditions (hypoxia) 0.0001), as well attenuated TGF-β mediated activation fibroblasts 0.0001). Quantitative profiling target cell following NV treatments revealed upregulation angiogenic proteins (MFGE8, MYH10, VDAC2) pro-survival (CNN2, THBS1, IGF2R) cardiomyocytes. In contrast, TGF-β-driven remodelling capacity (ACTN1, COL1A1/2/4A2/12A1, ITGA1/11, THBS1). This study presents approach generating functional repair.

Language: Английский

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Biochemical Aspects That Lead to Abusive Use of Trimetazidine in Performance Athletes: A Mini-Review

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1605 - 1605

Published: Jan. 28, 2024

Trimetazidine (TMZ), used for treating stable angina pectoris, has garnered attention in the realm of sports due to its potential performance-enhancing properties, and World Anti-Doping Agency (WADA) classified TMZ on S4 list prohibited substances since 2014. The purpose this narrative mini-review is emphasize biochemical aspects underlying abusive use among athletes as a metabolic modulator cardiac energy metabolism. myocardium’s ability adapt substrate utilization between glucose fatty acids crucial maintaining function under various conditions, such rest, moderate exercise, intense effort. acts partial inhibitor acid oxidation by inhibiting 3-ketoacyl-CoA thiolase (KAT), shifting production from long-chain glucose, reducing oxygen consumption, improving function, enhancing exercise capacity. Furthermore, modulates pyruvate dehydrogenase (PDH) activity, promoting while lowering lactate production, ultimately stabilizing myocardial function. TMZs role oxidative stress notable, it activates antioxidant enzymes like glutathione peroxidase (GSH-Px) superoxide dismutase (SOD). In conclusion, mechanisms make an attractive but controversial option seeking competitive edge.

Language: Английский

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Cinnamaldehyde activates AMPK/PGC-1α pathway via targeting GRK2 to ameliorate heart failure

Phytomedicine, Journal Year: 2024, Volume and Issue: 133, P. 155894 - 155894

Published: July 20, 2024

Language: Английский

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Treatment with recombinant Sirt1 rewires the cardiac lipidome and rescues diabetes-related metabolic cardiomyopathy

Cardiovascular Diabetology, Journal Year: 2023, Volume and Issue: 22(1)

Published: Nov. 13, 2023

Metabolic cardiomyopathy (MCM), characterized by intramyocardial lipid accumulation, drives the progression to heart failure with preserved ejection fraction (HFpEF). Although evidence suggests that mammalian silent information regulator 1 (Sirt1) orchestrates myocardial metabolism, it is unknown whether its exogenous administration could avoid MCM onset. We investigated chronic treatment recombinant Sirt1 (rSirt1) halt progression.db/db mice, an established model of MCM, were supplemented intraperitoneal rSirt1 or vehicle for 4 weeks and compared their db/ + heterozygous littermates. At end treatment, cardiac function was assessed ultrasound left ventricular samples collected processed molecular analysis. Transcriptional changes evaluated using a custom PCR array. Lipidomic analysis performed mass spectrometry. H9c2 cardiomyocytes exposed hyperglycaemia treated used as in vitro investigate ability directly target modulate malondialdehyde levels caspase 3 activity. Myocardial from diabetic nondiabetic patients analysed explore expression signaling pathways.rSirt1 restored performance improving fraction, fractional shortening diastolic (E/A ratio). In rSirt1-treated db/db modulated lipidome: medium long-chain triacylglycerols, triacylglycerols containing only saturated fatty acids reduced, while those docosahexaenoic acid increased. Mechanistically, several genes involved trafficking, metabolism inflammation, such Cd36, Acox3, Pparg, Ncoa3, Ppara downregulated both vivo. humans, reduced associated higher PPARG-related genes.In mouse supplementation rescued function. This modulation lipidome downregulation PPARG signaling. These findings confirmed human myocardium. Treatments increase may represent promising strategy prevent abnormalities development.

Language: Английский

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Fatty Acid Synthase Inhibition Offers Protection Against Pressure-Induced Cardiac Hypertrophy

Published: Jan. 1, 2025

PurposeDisturbed cardiac metabolism is an important aspect of pathology Cardiac hypertrophy (CH). Studies have shown a higher rate de novo fatty acid synthesis in HF and its inhibition has been protective. However, role CH still needs further clarification.MethodFor vitro studies, Phenylephrine (PE) was used to induce adult human ventricular cardiomyocytes (AC16). For vivo 2 kidney 1 clip (2K1C) Transverse aortic constriction (TAC) models rats were used. siRNA (30 nM) C75 (2 mg/kg, i.p. once week for 8 weeks) inhibited FAS vivo. Echocardiography histochemical staining observe remodeling. Western blotting, Seahorse analysis, fluorescence microscopy FACS performed detect metabolic alterations, mitochondrial dysfunction, protein hypertrophy.ResultIncreased expression activity observed PE exposed AC16 2K1C TAC rats. Inhibition decreased hypertrophy, by malonylation mTOR, apoptosis, glycolysis, oxidative stress restored phosphorylation cells. In rats, prevented remodelling models. It also increased ATP, ROS membrane potential the model rats,ConclusionThe results demonstrated that modulated during CH, through inhibition, it dysfunctions. The findings, therefore, suggest inhibiting may be new therapeutic approach treating patients.

Language: Английский

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Interplay between energy metabolism and NADPH oxidase-mediated pathophysiology in cardiovascular diseases

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 10, 2025

Sustained production of reactive oxygen species (ROS) and an imbalance in the antioxidant system have been implicated development cardiovascular diseases (CVD), especially when combined with diabetes, hypercholesterolemia, other metabolic disorders. Among them, NADPH oxidases (NOX), including NOX1-5, are major sources ROS that mediate redox signaling both physiological pathological processes, fibrosis, hypertrophy, remodeling. Recent studies demonstrated mitochondria produce more proteins energy response to adverse stress, corresponding increase superoxide radical anions. Novel NOX4-mediated modulatory mechanisms considered crucial for maintaining metabolism homeostasis during states. In this review, we integrate latest data elaborate on interactions between oxidative stress various CVD, aiming elucidate higher incidence CVD individuals Furthermore, correlations NOX ferroptosis, based metabolism, preliminarily discussed. Further discoveries these might promote novel therapeutic drugs targeting their crosstalk potentially offering efficient management strategies CVD.

Language: Английский

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Alterations in Lipid Saturation Trigger Remodeling of the Outer Mitochondrial Membrane

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 23, 2025

Lipid saturation is a key determinant of membrane function and organelle health, with changes in triggering adaptive quality control mechanisms to maintain integrity. Among cellular membranes, the mitochondrial outer (OMM) an important interface for many functions, but how lipid impacts OMM remains unclear. Here, we show that increased intracellular unsaturated fatty acids (UFAs) remodel by promoting formation multilamellar mitochondrial-derived compartments (MDCs), which sequester proteins lipids from OMM. These effects depend on incorporation UFAs into phospholipids, suggesting bilayer composition mediate this process. Furthermore, elevated impair assembly protein translocase (TOM) complex, unassembled TOM components captured MDCs. Collectively, these findings suggest alterations phospholipid may destabilize complexes trigger response excess through MDC formation. Mitochondrial-derived are structures metabolic perturbations, it largely unknown fluidity influences pathway.Increased levels phospholipids disrupt large multi-subunit complex membrane, promote compartments, while saturated inhibits compartments.These reveal link between stress driving compartment biogenesis, thus control.

Language: Английский

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