The Pathogenesis of Cardiac Fibrosis: A Review of Recent Progress

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(5), P. 2617 - 2617

Published: Feb. 27, 2022

Fibrosis is defined as the excessive deposition of extracellular matrix (ECM) proteins in interstitium. It an essential pathological response to chronic inflammation. ECM protein initially protective and critical for wound healing tissue regeneration. However, cardiac remodeling continuous damage with subsequent results a distorted organ architecture significantly impacts function. In this review, we summarized discussed histologic features fibrosis signaling factors that control it. We evaluated origin characteristic markers fibroblasts. also lymphatic vessels, which have become more important recent years improve fibrosis.

Language: Английский

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Triglyceride-glucose index (TyG) as a novel biomarker in the era of cardiometabolic medicine

International Journal of Cardiology, Journal Year: 2024, Volume and Issue: 418, P. 132663 - 132663

Published: Oct. 18, 2024

Language: Английский

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Doxorubicin induced immune abnormalities and inflammatory responses via HMGB1, HIF1-α and VEGF pathway in progressive of cardiovascular damage

Annals of Medicine and Surgery, Journal Year: 2022, Volume and Issue: 76

Published: March 21, 2022

Doxorubicin (DOX) is a commonly used treatment for cancer and the mechanism of DOX-induced cardiomyocyte damage in cardiovascular disease not fully understood. High-mobility group box 1 (HMGB1), strong induce proinflammatory cytokines via associated molecular pattern (DAMP) which its interaction with receptor advanced glycation end products (RAGE), that affect cytokine release, angiogenesis role HMBG1, HIF-1α VEGF as an important regulator these cardiac failure processes. Hypoxia-inducible factor-1α (HIF-1α) plays cellular response to systemic oxygen levels cells angiogenic factor can stimulate responses on surface endothelial will be described.The aim this article comprehensively review HMGB1, HIF-1α, Cardiovascular Disease mechanisms.The data study were collect by search keyword combinations medical subject headings (MeSH) "HMGB1", "HIF-1 α", "VEGF", "DOX" "Cardiovascular disease" relevant reference lists manually searched PubMed, EMBASE Scopus database. All articles base above included narratively discussed article.Several revealed mechanisms DOX related may potential prevention intervention.HMGB1, has pivotal DOX-induce predominantly acts through different pathways. The HMGB1 myocardial suggests mediator damage. In addition, inhibit activity where decrease expression also responsible upregulation several factors, including VEGF. anti-angiogenesis both vitro vivo reduces side effects markedly. administration show inhibitory effect mediated signaling pathway triggered cells.

Language: Английский

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Exploring the Complex Relationship between Diabetes and Cardiovascular Complications: Understanding Diabetic Cardiomyopathy and Promising Therapies

Biomedicines, Journal Year: 2023, Volume and Issue: 11(4), P. 1126 - 1126

Published: April 7, 2023

Diabetes mellitus (DM) and cardiovascular complications are two unmet medical emergencies that can occur together. The rising incidence of heart failure in diabetic populations, addition to apparent coronary disease, ischemia, hypertension-related complications, has created a more challenging situation. Diabetes, as predominant cardio-renal metabolic syndrome, is related severe vascular risk factors, it underlies various complex pathophysiological pathways at the molecular level progress converge toward development cardiomyopathy (DCM). DCM involves several downstream cascades cause structural functional alterations heart, such diastolic dysfunction progressing into systolic dysfunction, cardiomyocyte hypertrophy, myocardial fibrosis, subsequent over time. effects glucagon-like peptide-1 (GLP-1) analogues sodium-glucose cotransporter-2 (SGLT-2) inhibitors on (CV) outcomes diabetes have shown promising results, including improved contractile bioenergetics significant benefits. purpose this article highlight pathophysiological, metabolic, contribute its cardiac morphology functioning. Additionally, will discuss potential therapies may be available future.

Language: Английский

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Inflammation across the spectrum of hypertrophic cardiac phenotypes

Heart Failure Reviews, Journal Year: 2023, Volume and Issue: 28(5), P. 1065 - 1075

Published: April 28, 2023

The hypertrophic cardiomyopathy phenotype encompasses a heterogeneous spectrum of genetic and acquired diseases characterized by the presence left ventricular hypertrophy in absence abnormal cardiac loading conditions. This "umbrella diagnosis" includes "classic" (HCM), due to sarcomere protein gene mutations, its phenocopies caused intra- or extracellular deposits, such as Fabry disease (FD) amyloidosis (CA). All these conditions share wide phenotypic variability which results from combination environmental factors whose pathogenic mediators are poorly understood so far. Accumulating evidence suggests that inflammation plays critical role broad cardiovascular conditions, including cardiomyopathies. Indeed, can trigger molecular pathways contribute cardiomyocyte dysfunction, matrix accumulation, microvascular dysfunction. Growing systemic is possible key pathophysiologic process potentially involved pathogenesis progression, influencing severity clinical outcome, heart failure. In this review, we summarize current knowledge regarding prevalence, significance, potential therapeutic implications HCM two most important phenocopies, FD CA.

Language: Английский

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Non-coding RNAs affecting NLRP3 inflammasome pathway in diabetic cardiomyopathy: a comprehensive review of potential therapeutic options

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

Published: Feb. 28, 2025

Cardiomyopathies are a heterogeneous group of disorders that can lead to fulminant heart failure and sudden cardiac death. In recent years, the prevalence all types cardiomyopathies has shown an upward trend globally. Up 40% patients with cardiomyopathy-related have diabetes mellitus (DM). With fast global spread DM, DCM is increasing accordingly it remains leading cause morbidity mortality in chronic diabetic patients. NLRP3 inflammasome significantly contributes development pathological progression DCM. Targeting or any mediators along its activation pathway provides new potential therapeutic targets for developing specialized drugs treat this comprehensive review, we sought introduce summarize non-coding RNAs effects targeting signaling We hope general overview aid future research therapies

Language: Английский

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Interleukin-6 and Cardiovascular and Kidney Outcomes in Patients With Type 2 Diabetes: New Insights From CANVAS

Diabetes Care, Journal Year: 2022, Volume and Issue: 45(11), P. 2644 - 2652

Published: Sept. 22, 2022

OBJECTIVE The inflammatory cytokine interleukin-6 (IL-6) is associated with cardiovascular (CV) and kidney outcomes in various populations. However, data patients type 2 diabetes are limited. We assessed the association of IL-6 CV Canagliflozin Cardiovascular Assessment Study (CANVAS) determined effect canagliflozin on IL-6. RESEARCH DESIGN AND METHODS Patients at high risk were randomly assigned to or placebo. Plasma was measured baseline years 1, 3, 6. composite outcome nonfatal myocardial infarction, stroke, death; sustained ≥40% estimated glomerular filtration rate decline, end-stage disease, kidney-related death. Multivariable-adjusted Cox proportional hazards regression used estimate associations between outcomes. over time a repeated-measures mixed-effects model. RESULTS geometric mean baseline, available 3,503 (80.2%) participants, 1.7 pg/mL. Each doubling 14% (95% CI 4, 24) 21% 45) increased outcomes, respectively. Over 6 years, by 5.8% 3.4, 8.3) placebo group. modestly attenuated increase (absolute percentage difference vs. 4.4% [95% 1.3, 9.9; P = 0.01]). At year each 25% lower level compared 7% 22) 5, risks for outcome, CONCLUSIONS In risk, its 1-year change IL-6–lowering therapy CV, kidney, safety remains be tested.

Language: Английский

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Serum Metabolomics Analysis of the Anti-Inflammatory Effects of Gallic Acid on Rats With Acute Inflammation

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: March 22, 2022

Background: Gallic acid (GA) is a natural small-molecule polyphenol having wide range of pharmacological activities. Until now, some works have studied the effect and mechanisms GA against inflammation. However, whether or how gallic regulates downstream metabolic disorder acute inflammation remains unclear. The present study explored protective potential mechanism on through metabolomics approach. Methods: An rat model was induced by local injection carrageenin. Local swelling paw serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) were assessed in Control, Model groups, respectively. Serum based high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS) also established to collect rats' profiles explore changes related pretreatment. Results: Compared Modal group, pain, redness, carrageenin significantly alleviated groups addition dose-dependent decreases TNF-α IL-6. Metabolomics analysis found significant alterations signatures between carrageenin-induced control groups. Twelve biomarkers further identified principal component (PCA) partial least squares discrimination (PLS-DA). In addition, when rats pretreated acid, levels eleven observed restore partially. Metabolic pathway networks revealed that might invert pathological process regulating key involved linoleic metabolism, ascorbate aldarate pentose glucuronate interconversions, arachidonic (AA) metabolism pathways. Conclusion: elucidates its possible from metabolomic perspective. These results could provide theoretical basis for clarifying acid's medicinal value curing clinic.

Language: Английский

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Single-Cell RNA Sequencing Reveals Metabolic Stress-Dependent Activation of Cardiac Macrophages in a Model of Dyslipidemia-Induced Diastolic Dysfunction

Circulation, Journal Year: 2023, Volume and Issue: 150(19), P. 1517 - 1532

Published: Dec. 21, 2023

BACKGROUND: Metabolic distress is often associated with heart failure preserved ejection fraction (HFpEF) and represents a therapeutic challenge. Metabolism-induced systemic inflammation links comorbidities HFpEF. How metabolic changes affect myocardial in the context of HFpEF not known. METHODS: We found that ApoE knockout mice fed Western diet recapitulate many features Single-cell RNA sequencing was used for expression analysis CD45 + cardiac cells to evaluate involvement diastolic dysfunction. focused bioinformatics on macrophages, obtaining high-resolution identification subsets these heart, enabling us study outcomes macrophage infiltrate identify macrophage-to-cardiomyocyte regulatory axis. To test whether clinically relevant sodium glucose cotransporter-2 inhibitor could ameliorate immune profile our model, were randomized receive dapagliflozin or vehicle 8 weeks. RESULTS: presented reduced function, exercise tolerance, increased pulmonary congestion lipid overload polyunsaturated fatty acids. The main cell types infiltrating included 4 subpopulations resident monocyte-derived determining proinflammatory exclusively knockout-Western mice. Lipid had direct effect inflammatory gene activation mediated through endoplasmic reticulum stress pathways. Investigation axis revealed potential effects cardiomyocytes multiple cytokines secreted by affecting pathways such as hypertrophy, fibrosis, autophagy. Finally, we describe an anti-inflammatory inhibition this model. CONCLUSIONS: Using single-cell model dysfunction driven hyperlipidemia, have determined cells, particular suggest inhibitors agents targeting specific phenotype

Language: Английский

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Discovery of a novel 1,3,4-oxadiazol-2-one-based NLRP3 inhibitor as a pharmacological agent to mitigate cardiac and metabolic complications in an experimental model of diet-induced metaflammation

European Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 257, P. 115542 - 115542

Published: June 3, 2023

Inspired by the recent advancements in understanding binding mode of sulfonylurea-based NLRP3 inhibitors to sensor protein, we developed new replacing central sulfonylurea moiety with different heterocycles. Computational studies evidenced that some designed compounds were able maintain important interaction within NACHT domain target protein similarly most active inhibitors. Among studied compounds, 1,3,4-oxadiazol-2-one derivative 5 (INF200) showed promising results being prevent NLRP3-dependent pyroptosis triggered LPS/ATP and LPS/MSU 66.3 ± 6.6% 61.6 11.5% reduce IL-1β release (35.5 8.8% μM) at 10 μM human macrophages. The selected compound INF200 (20 mg/kg/day) was then tested an vivo rat model high-fat diet (HFD)-induced metaflammation evaluate its beneficial cardiometabolic effects. significantly counteracted HFD-dependent "anthropometric" changes, improved glucose lipid profiles, attenuated systemic inflammation biomarkers cardiac dysfunction (particularly BNP). Hemodynamic evaluation on Langendorff indicate limited myocardial damage-dependent ischemia/reperfusion injury (IRI) improving post-ischemic systolic recovery attenuating contracture, infarct size, LDH release, thus reversing exacerbation obesity-associated damage. Mechanistically, hearts, IFN200 reduced IRI-dependent activation, inflammation, oxidative stress. These highlight potential novel inhibitor, INF200, ability reverse unfavorable cardio-metabolic associated obesity.

Language: Английский

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