Metabolism, Journal Year: 2023, Volume and Issue: 146, P. 155658 - 155658
Published: July 9, 2023
Language: Английский
Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)
Published: March 20, 2023
Metabolic abnormalities lead to the dysfunction of metabolic pathways and metabolite accumulation or deficiency which is well-recognized hallmarks diseases. Metabolite signatures that have close proximity subject's phenotypic informative dimension, are useful for predicting diagnosis prognosis diseases as well monitoring treatments. The lack early biomarkers could poor serious outcomes. Therefore, noninvasive methods with high specificity selectivity desperately needed. Small molecule metabolites-based metabolomics has become a specialized tool biomarker pathway analysis, revealing possible mechanisms human various deciphering therapeutic potentials. It help identify functional related variation delineate biochemical changes indicators pathological damage prior disease development. Recently, scientists established large number profiles reveal underlying networks target exploration in biomedicine. This review summarized analysis on potential value small-molecule candidate metabolites clinical events, may better diagnosis, prognosis, drug screening treatment. We also discuss challenges need be addressed fuel next wave breakthroughs.
Language: Английский
Citations
388
Molecular & Cellular Proteomics, Journal Year: 2023, Volume and Issue: 22(6), P. 100561 - 100561
Published: April 28, 2023
The world has witnessed a steady rise in both non-infectious and infectious chronic diseases, prompting cross-disciplinary approach to understand treating disease. Current medical care focuses on people after they become patients rather than preventing illness, leading high costs late-stage diseases. Additionally, "one-size-fits all" health does not take into account individual differences genetics, environment, or lifestyle factors, decreasing the number of benefiting from interventions. Rapid advances omics technologies progress computational capabilities have led development multi-omics deep phenotyping, which profiles interaction multiple levels biology over time empowers precision approaches. This review highlights current emerging modalities for discusses applications following areas: genetic variation, cardio-metabolic cancer, organ transplantation, pregnancy, longevity/aging. We will briefly discuss potential approaches disentangling host-microbe host-environmental interactions. touch areas electronic record clinical imaging integration with muti-omics health. Finally, we challenges implementation its future prospects.
Language: Английский
Citations
159
Biomolecules, Journal Year: 2022, Volume and Issue: 12(12), P. 1891 - 1891
Published: Dec. 17, 2022
Mitochondria calcium is a double-edged sword. While low levels of are essential to maintain optimal rates ATP production, extreme overcoming the mitochondrial retention capacity leads loss function. In moderate amounts, however, synthesis inhibited in calcium-titratable manner. consequences overload well-known, effects on function moderately loaded range remain enigmatic. These observations associated with changes mitochondria ultrastructure and cristae network. The present mini review/perspective follows up previous studies using well-established cryo–electron microscopy poses an explanation for observable depressed during calcium-overloaded states. results presented herein suggest that inhibition oxidative phosphorylation not caused by direct decoupling energy metabolism via opening calcium-sensitive, proteinaceous pore but rather separate related calcium-dependent phenomenon. Such states points towards ultrastructural modifications, enzyme activity changes, or interplay between both events.
Language: Английский
Citations
94
European Heart Journal, Journal Year: 2023, Volume and Issue: 44(13), P. 1170 - 1185
Published: Jan. 12, 2023
Abstract Aims Genetic hypertrophic cardiomyopathy (HCM) is caused by mutations in sarcomere protein-encoding genes (i.e. genotype-positive HCM). In an increasing number of patients, HCM occurs the absence a mutation genotype-negative Mitochondrial dysfunction thought to be key driver pathological remodelling HCM. Reports mitochondrial respiratory function and specific disease-modifying treatment options patients with are scarce. Methods results Respirometry was performed on septal myectomy tissue from (n = 59) evaluate oxidative phosphorylation fatty acid oxidation. most notably reflected impaired NADH-linked respiration. but not respiration markedly depressed indexed thickness ≥10 compared <10. explained reduced abundance or fragmentation mitochondria, as evaluated transmission electron microscopy. Rather, improper organization mitochondria relative myofibrils (expressed percentage disorganized mitochondria) strongly associated dysfunction. Pre-incubation cardiolipin-stabilizing drug elamipretide raising NAD+ levels both boosted Conclusion cardiomyocyte architecture disruption linked hypertrophy Despite severe myocardial were responsive treatments aimed at restoring function, eliciting target prevent ameliorate cardiac disease Mitochondria-targeting therapy may particularly benefit HCM, given tight link between impairment thickening this subpopulation.
Language: Английский
Citations
53
Circulation Research, Journal Year: 2024, Volume and Issue: 135(2), P. 372 - 396
Published: July 4, 2024
Despite clinical and scientific advancements, heart failure is the major cause of morbidity mortality worldwide. Both mitochondrial dysfunction inflammation contribute to development progression failure. Although crucial reparative healing following acute cardiomyocyte injury, chronic damages heart, impairs function, decreases cardiac output. Mitochondria, which comprise one third volume, may prove a potential therapeutic target for Known primarily energy production, mitochondria are also involved in other processes including calcium homeostasis regulation cellular apoptosis. Mitochondrial function closely related morphology, alters through dynamics, thus ensuring that needs cell met. However, failure, changes substrate use lead impaired myocyte function. This review discusses cristae role contact site organizing system complex ultrastructure changes. Additionally, this covers mitochondria-endoplasmic reticulum sites, communication via nanotunnels, altered metabolite production during We highlight these often-neglected factors promising targets
Language: Английский
Citations
34
Medicina, Journal Year: 2024, Volume and Issue: 60(1), P. 94 - 94
Published: Jan. 3, 2024
Pediatric cardiomyopathies (CMs) and electrical diseases constitute a heterogeneous spectrum of disorders distinguished by structural abnormalities in the heart muscle, attributed to genetic variant. They rank among main causes morbidity mortality pediatric population, with an annual incidence 1.1–1.5 per 100,000 children under age 18. The most common conditions are dilated cardiomyopathy (DCM) hypertrophic (HCM). Despite great enthusiasm for research this field, studies population still limited, management treatment often follow adult recommendations, which have significantly more data on benefits. Although cardiac share similar morphological clinical manifestations, their outcomes differ. This review summarizes latest evidence genetics, characteristics, management, updated primary CMs diseases, including DCM, HCM, arrhythmogenic right ventricular (ARVC), Brugada syndrome (BrS), catecholaminergic polymorphic tachycardia (CPVT), long QT (LQTS), short (SQTS).
Language: Английский
Citations
27
Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)
Published: June 4, 2024
Abstract Semaglutide, a glucagon-like peptide-1 receptor agonist, is clinically used as glucose-lowering and weight loss medication due to its effects on energy metabolism. In heart failure, production impaired altered mitochondrial function increased glycolysis. However, the impact of semaglutide cardiomyocyte metabolism under pressure overload remains unclear. Here we demonstrate that improves cardiac reduces hypertrophy fibrosis in mouse model overload-induced failure. Semaglutide preserves structure chronic stress. Metabolomics reveals damage, lipid accumulation, ATP deficiency by promoting pyruvate entry into tricarboxylic acid cycle increasing fatty oxidation. Transcriptional analysis shows regulates myocardial through Creb5/NR4a1 axis PI3K/AKT pathway, reducing NR4a1 expression translocation mitochondria. knockdown ameliorates dysfunction abnormal glucose heart. These findings suggest may be therapeutic agent for improving remodeling modulating
Language: Английский
Citations
26
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
Citations
2
International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(24), P. 16053 - 16053
Published: Dec. 16, 2022
High mortality rates due to cardiovascular diseases (CVDs) have attracted worldwide attention. It has been reported that mitochondrial dysfunction is one of the most important mechanisms affecting pathogenesis CVDs. Mitochondrial DNA (mtDNA) mutations may result in impaired oxidative phosphorylation (OXPHOS), abnormal respiratory chains, and ATP production. In dysfunctional mitochondria, electron transport chain (ETC) uncoupled energy supply reduced, while reactive oxygen species (ROS) production increased. Here, we discussed analyzed relationship between mtDNA mutations, mitophagy, decreased OXPHOS, elevated ROS, CVDs from perspective dysfunction. Furthermore, explored current potential therapeutic strategies for by eliminating (e.g., editing replacement), enhancing improving OXPHOS capacity supplement with NAD+, nicotinamide riboside (NR), mononucleotide (NMN), nano-drug delivery), reducing ROS Coenzyme Q10 other antioxidants), dissected their respective advantages limitations. fact, some are still a long way achieving safe effective clinical treatment. Although establishing remains challenging, starting holds bright prospects.
Language: Английский
Citations
67
Circulation Heart Failure, Journal Year: 2022, Volume and Issue: 15(6)
Published: May 11, 2022
Background: Defects in energetics are thought to be central the pathophysiology of hypertrophic cardiomyopathy (HCM); yet, determinants ATP availability not known. The purpose this study is ascertain nature and extent metabolic reprogramming human HCM, its potential impact on contractile function. Methods: We conducted proteomic targeted, quantitative metabolomic analyses heart tissue from patients with HCM nonfailing control hearts. Results: In analysis, greatest differences observed samples compared controls were increased abundances extracellular matrix intermediate filament proteins decreased muscle creatine kinase mitochondrial involved fatty acid oxidation. These protein abundance coupled marked reductions acyl carnitines, byproducts oxidation, samples. Conversely, ketone body 3-hydroxybutyrate, branched chain amino acids, their breakdown products, all significantly content, phosphocreatine, nicotinamide adenine dinucleotide phosphate derivatives, NADP NADPH, acetyl CoA also severely reduced Functional assays performed skinned myocardial fibers demonstrated that magnitude reduction content would expected decrease rate cross-bridge detachment. Moreover, left atrial size, an indicator diastolic compliance, was inversely correlated hearts HCM. Conclusions: display profound deficits nucleotide markedly capacity for oxidation increases bodies acids. results have important therapeutic implications future design modulators treat
Language: Английский
Citations
60