SGLT2 inhibitors: role in protective reprogramming of cardiac nutrient transport and metabolism

Nature Reviews Cardiology, Journal Year: 2023, Volume and Issue: 20(7), P. 443 - 462

Published: Jan. 6, 2023

Language: Английский

---

MCT4-dependent lactate transport: a novel mechanism for cardiac energy metabolism injury and inflammation in type 2 diabetes mellitus

Cardiovascular Diabetology, Journal Year: 2024, Volume and Issue: 23(1)

Published: March 14, 2024

Abstract Diabetic cardiomyopathy (DCM) is a major contributor to mortality in diabetic patients, characterized by multifaceted pathogenesis and limited therapeutic options. While lactate, byproduct of glycolysis, known be significantly elevated type 2 diabetes, its specific role DCM remains uncertain. This study reveals an abnormal upregulation monocarboxylate transporter 4 (MCT4) on the plasma membrane cardiomyocytes leading excessive lactate efflux from these cells. The disruption transport homeostasis perturbs intracellular lactate-pyruvate balance cardiomyocytes, resulting oxidative stress inflammatory responses that exacerbate myocardial damage. Additionally, our findings suggest increased augments histone H4K12 lactylation macrophages, facilitating infiltration within microenvironment. In vivo experiments have demonstrated inhibiting MCT4 effectively alleviates pathological damage, reduces macrophage infiltration, enhances cardiac function mice. Furthermore, clinical prediction model has been established, demonstrating notable association between peripheral blood levels diastolic dysfunction individuals with diabetes. underscores potential as prognostic biomarker for DCM. Ultimately, highlight pivotal involvement dysregulation energy metabolism macrophage-mediated inflammation These insights offer novel perspectives pave way development targeted strategies against this debilitating condition.

Language: Английский

---

Molecular Regulation of Cardiomyocyte Maturation

Current Cardiology Reports, Journal Year: 2025, Volume and Issue: 27(1)

Published: Jan. 21, 2025

Language: Английский

---

The role of glycolytic metabolic pathways in cardiovascular disease and potential therapeutic approaches

Basic Research in Cardiology, Journal Year: 2023, Volume and Issue: 118(1)

Published: Nov. 8, 2023

Abstract Cardiovascular disease (CVD) is a major threat to human health, accounting for 46% of non-communicable deaths. Glycolysis conserved and rigorous biological process that breaks down glucose into pyruvate, its primary function provide the body with energy intermediate products needed life activities. The non-glycolytic actions enzymes associated glycolytic pathway have long been found be development CVD, typically exemplified by metabolic remodeling in heart failure, which condition exhibits rapid adaptive response hypoxic conditions, occurring early course failure. It mainly characterized decrease oxidative phosphorylation rise pathway, glycolysis considered hallmark remodeling. In addition this, main source cardiomyocytes during ischemia–reperfusion. Not only that, auxiliary pathways glycolysis, such as polyol hexosamine pentose phosphate are also closely related CVD. Therefore, targeting very attractive therapeutic intervention However, relationship between CVD complex, some preclinical studies confirmed does certain degree efficacy, but specific role has yet explored. This article aims summarize current knowledge regarding key (including hexokinase (HK), phosphoglucose isomerase (PGI), phosphofructokinase-1 (PFK1), aldolase (Aldolase), phosphoglycerate metatase (PGAM), enolase (ENO) pyruvate kinase (PKM) lactate dehydrogenase (LDH)) their cardiovascular diseases (e.g., myocardial infarction, atherosclerosis) possible emerging targets.

Language: Английский

---

Metabolic Reprogramming: A Byproduct or a Driver of Cardiomyocyte Proliferation?

Circulation, Journal Year: 2024, Volume and Issue: 149(20), P. 1598 - 1610

Published: May 13, 2024

Defining mechanisms of cardiomyocyte proliferation should guide the understanding endogenous cardiac regeneration and could lead to novel treatments for diseases such as myocardial infarction. In neonatal heart, energy metabolic reprogramming (phenotypic alteration glucose, fatty acid, amino acid metabolism) parallels cell cycle arrest cardiomyocytes. The occurring shortly after birth is associated with alterations in blood oxygen levels, substrate availability, hemodynamic stress, hormone release. adult infarction causes but these changes cannot stimulate sufficient replace those lost by ischemic injury. Some putative pro-proliferative interventions can induce reprogramming. Recent data show that altering enzymes PKM2 [pyruvate kinase 2], LDHA [lactate dehydrogenase A], PDK4 4], SDH [succinate dehydrogenase], CPT1b [carnitine palmitoyl transferase 1b], or HMGCS2 [3-hydroxy-3-methylglutaryl-CoA synthase 2] partially reverse promotes proliferation. How regulates not clearly defined. possible involve biosynthetic pathways from glycolysis shunts epigenetic regulation induced intermediates. Metabolic manipulation represent a new approach regeneration; however, efficacy manipulations requires optimization, molecular targets need be this review, we summarize features, triggers, regulatory networks responsible discuss current critical determinant

Language: Английский

---

The Impact of the Competition on miRNA, Proteins, and Metabolites in the Blood Exosomes of the Yili Horse

Genes, Journal Year: 2025, Volume and Issue: 16(2), P. 224 - 224

Published: Feb. 15, 2025

Horse racing may cause stress-induced physiological changes and tissue damage in horses, but the miRNA expression, protein metabolic substances plasma exosomes of Yili horse after are still unclear. This study detected miRNA, horses before competition, providing new insights for post-race recovery care horses. Eight three-year-old that had undergone training were selected as research subjects, with four not competed control group participated competition half an hour group. Extract whole blood separate from two groups then extract exosomes; MiRNAs, proteins, metabolites extracellular vesicles analyzed using miRNAomics, proteomics, metabolomics. P Result: After levels miRNAs related to cytoplasm nucleus increased, transcription transcriptional regulation biological processes significantly increased. The proteins also cell signaling function carbohydrates their reduced. process causes significant metabolomics which mainly regulation.

Language: Английский

---

Foetal recapitulation of nutrient surplus signalling by O‐GlcNAcylation and the failing heart

European Journal of Heart Failure, Journal Year: 2023, Volume and Issue: 25(8), P. 1199 - 1212

Published: July 12, 2023

The development of the foetal heart is driven by increased glucose uptake and activation mammalian target rapamycin (mTOR) hypoxia-inducible factor-1α (HIF-1α), which drives glycolysis. In contrast, healthy adult governed sirtuin-1 (SIRT1) adenosine monophosphate-activated protein kinase (AMPK), promote fatty-acid oxidation substantial mitochondrial ATP production required for survival in a high-workload normoxic environment. During cardiac injury, recapitulates signalling programme, (although adaptive short term) highly deleterious if sustained long periods time. Prolonged increases cardiomyocytes under stress leads to flux through hexosamine biosynthesis pathway; its endproduct - uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) functions as critical nutrient surplus sensor. UDP-GlcNAc post-translational modification known O-GlcNAcylation, rapidly reversibly modifies thousands intracellular proteins. Both O-GlcNAcylation phosphorylation act at serine/threonine residues, but whereas regulated hundreds specific kinases phosphatases, only two enzymes, O-GlcNAc transferase (OGT) O-GlcNAcase (OGA), adds or removes GlcNAc (N-acetylglucosamine), respectively, from Recapitulation programming failure (regardless diabetes) accompanied marked both experimentally clinically. Heightened impaired calcium kinetics contractile derangements, arrhythmias related voltage-gated sodium channels Ca2+ /calmodulin-dependent II, dysfunction, maladaptive hypertrophy, microvascular fibrosis cardiomyopathy. These effects can be prevented suppression achieved upregulation AMPK SIRT1 pharmacological inhibition OGT stimulation OGA. sodium-glucose cotransporter 2 (SGLT2) inhibitors on are reduced their cytoprotective reportedly abrogated action suppress blocked. Such an may represent one many mechanisms enhanced following SGLT2 cardiovascular benefits. observations, taken collectively, suggest that sensor (which acting concert with mTOR HIF-1α)

Language: Английский

---

The Structure of the Cardiac Mitochondria Respirasome Is Adapted for the β-Oxidation of Fatty Acids

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 2410 - 2410

Published: Feb. 18, 2024

It is well known that in the heart and kidney mitochondria, more than 95% of ATP production supported by β-oxidation long-chain fatty acids. However, acids mitochondria has been studied much less substrates formed during catabolism carbohydrates amino In last few decades, several discoveries have made are directly related to acid oxidation. this review, we an attempt re-evaluate from perspectives new discoveries. The single set electron transporters cardiac mitochondrial respiratory chain organized into three supercomplexes. Two them contain complex I, a dimer III, two dimers IV. third, smaller supercomplex contains III We also considered other important First, enzymes physically associated with respirasome. Second, creates highest level QH2 reverses flow electrons through II, reducing fumarate succinate. Third, greatly stimulated presence argue respirasome uniquely adapted for acyl-CoA dehydrogenase reduces membrane’s pool ubiquinone QH2, which instantly oxidized supercomplex, generating high energization reversing increasing NADH/NAD+ ratio matrix. nicotinamide nucleotide transhydrogenase catalyzes hydride (H-, proton plus electrons) transfer across inner membrane, cytosolic NADP(H), thus providing muscle contraction energy equivalents housekeeping processes.

Language: Английский

---

Cardiac Regeneration in Adult Zebrafish: A Review of Signaling and Metabolic Coordination

Current Cardiology Reports, Journal Year: 2025, Volume and Issue: 27(1)

Published: Jan. 10, 2025

Language: Английский

---

Geriatric nutritional risk index as a predictor of 30-day and 365-day mortality in patients with acute myocardial infarction: a retrospective cohort study using the MIMIC-IV database

Frontiers in Nutrition, Journal Year: 2025, Volume and Issue: 12

Published: Feb. 5, 2025

Background The Geriatric Nutritional Risk Index (GNRI) is a clinical indicator for evaluating the nutritional status of patients, but its role in short-term prognosis patients with acute myocardial infarction still not fully understood. This study aims to explore correlation between GNRI and overall mortality within 30 days 365 those (AMI). Methods A retrospective analysis was performed utilizing Medical Information Mart Intensive Care IV (MIMIC-IV) database. included 895 diagnosed AMI identified through ICD9 ICD10 codes (410, I21, I23) who were hospitalized first time due AMI. Subjects classified into four groups according GNRI: high (GNRI <82, n = 110), moderate (82 ≤ <92, 205), low (92 <98, 225), no risk ≥98, 355). Restricted cubic splines (RCS) threshold effect analyses applied non-linear relationship mortality. Subgroup conducted based on gender, hypertension, diabetes, stroke, hyperlipidemia, chronic obstructive pulmonary disease, age. mediation investigate impact lymphocytes association Results In an sample elevated correlated reduced 30-day (HR 0.937, 95% CI: 0.917–0.957, p < 0.001) 365-day 0.923–0.950, 0.001). trend categories indicated significant decline associated rising (P <0.001). validated consistency such results throughout diverse patient characteristics. significantly mediated (ACME: 0.022, 0.003–0.180, landmark at 20 after admission further demonstrated during different phases recovery. Conclusion highlights prognostic value predicting long-term emphasizing significance inflammatory indicators therapy assessment these individuals.

Language: Английский

---