International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 142471 - 142471
Published: March 1, 2025
Language: Английский
Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(10)
Published: Oct. 20, 2023
Abstract Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of fatty deposits in inner walls vessels. These plaques restrict blood flow and lead to complications such as heart attack or stroke. The development atherosclerosis influenced variety factors, including age, genetics, lifestyle, underlying health conditions high pressure diabetes. Atherosclerotic stable form are slow growth, which leads luminal stenosis, with low embolic potential unstable form, contributes risk for thrombotic rapid clinical onset. In this complex scenario atherosclerosis, macrophages participate whole process, initiation, growth eventually rupture wound healing stages artery plaque formation. Macrophages exhibit heterogeneity plasticity, affect evolving microenvironment, e.g., leading excessive lipid accumulation, cytokine hyperactivation, hypoxia, apoptosis necroptosis. metabolic functional transitions response microenvironmental factors not only influence ongoing imminent responses within lesions but also directly dictate atherosclerotic progression regression. review, we discuss origin plaques, their phenotypic diversity, shifts, fate roles they play dynamic atherosclerosis. It describes how interact other cells, particularly T cells. Ultimately, targeting pathways involved macrophage polarization may innovative promising approaches precision medicine. Further insights into landscape biological features offer valuable information optimizing future treatment macrophages.
Language: Английский
Citations
120
European Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 966, P. 176338 - 176338
Published: Jan. 17, 2024
Inflammation drives coronary artery disease and atherosclerosis implications. Lipoprotein entry, retention, oxidative modification cause endothelial damage, triggering innate adaptive immune responses. Recruited cells orchestrate the early atherosclerotic lesions by releasing proinflammatory cytokines, expediting foam cell formation, intraplaque haemorrhage, secretion of matrix-degrading enzymes, lesion progression, eventually promoting syndrome via various inflammatory cascades. In addition, soluble mediators disrupt dynamic anti- prothrombotic balance maintained pave way for such as angina pectoris. Recent studies have established a relationship between elevated levels markers, including C-reactive protein (CRP), interleukins (IL-6, IL-1β), tumour necrosis factor-alpha (TNF-α) with severity CAD possibility future cardiovascular events. High-sensitivity (hs-CRP) is marker assessing systemic inflammation predicting risk developing based on its peak plasma levels. Hence, understanding cross-talk interactions inflammation, atherogenesis, highly warranted to recalculate factors that activate propagate arterial devise therapeutic strategies accordingly. Cholesterol-inflammation lowering agents (statins), monoclonal antibodies targeting IL-1 IL-6 (canakinumab tocilizumab), disease-modifying antirheumatic drugs (methotrexate), sodium-glucose transport protein-2 (SGLT2) inhibitors, colchicine xanthene oxidase inhibitor (allopurinol) shown promising results in reducing regressing atherogenic plaque modifying course CAD. Here, we review complex interplay inflammatory, endothelial, smooth muscle cells. Moreover, putative role CAD, underlying mechanisms potential implications are also discussed herein.
Language: Английский
Citations
66
Nature Metabolism, Journal Year: 2023, Volume and Issue: 5(3), P. 431 - 444
Published: Feb. 16, 2023
Language: Английский
Citations
59
Circulation Research, Journal Year: 2024, Volume and Issue: 134(2), P. 165 - 185
Published: Jan. 3, 2024
Atherosclerosis is a globally prevalent chronic inflammatory disease with high morbidity and mortality. The development of atherosclerotic lesions determined by macrophages. This study aimed to investigate the specific role myeloid-derived CD147 (cluster differentiation 147) in atherosclerosis its translational significance.
Language: Английский
Citations
36
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
Citations
25
Theranostics, Journal Year: 2024, Volume and Issue: 14(6), P. 2427 - 2441
Published: Jan. 1, 2024
Background: MER proto-oncogene tyrosine kinase (MerTK) is a key receptor for efferocytosis, process the clearance of apoptotic cells.MerTK mainly expressed in macrophages and immature dendritic cells.There are very limited reports focused on MerTK biology aortic endothelial cells (ECs).It remains unclear role blood flow patterns regulating MerTK-mediated efferocytosis ECs.This study was designed to investigate whether EC respond during atherosclerosis.Methods: Big data analytics, RNA-seq proteomics combined with our vitro vivo studies were applied reveal potential molecular mechanisms.Partial carotid artery ligation AAV-PCSK9 high fat diet used set up acute atherosclerosis 4 weeks.Results: Our showed that sensitive inhibited by disturbed oscillatory shear stress primary human ECs (HAECs).The HAECs incubated d-flow promotes pro-inflammatory pathway senescence pathway.Our immunostaining that, compared WT group, -/-aggravates areas through upregulation dysfunction markers (e.g.IL-1β, NF-κB, TLR4, MAPK signaling, vWF, VCAM-1 p22 phox ) mitochondrial dysfunction.Interestingly, -/-induces obvious abnormal thickening accompanied decreased promoting development atherosclerosis.Conclusions: suggests play an important ECs, revealing new promising therapeutic strategy restoration against atherosclerosis.
Language: Английский
Citations
12
Physiological Reports, Journal Year: 2025, Volume and Issue: 13(1)
Published: Jan. 1, 2025
Abstract Inflammation and a metabolic shift from oxidative metabolism to glycolysis are common in the ischemic heart, latter partly controlled by pyruvate kinase (muscle, PKM). We previously identified alternative splicing promoting PKM2 isoform after myocardial infarction (MI). examined role of physiological upregulation MI, modeled ligation left anterior descending coronary artery, using global knockout (PKM2 −/− ) mice. Echocardiography showed similar cardiac function between control mice MI. However, infarcted hearts had increased abundances transcripts associated with stress immune responses. Immunohistochemistry revealed greater abundance macrophages prior small increase CD86 + hearts. Elevated baseline plasma IL‐6, IL‐1β, C‐reactive protein, 3 days post‐MI, were observed Oxidative lipid products also elevated hearts, while antioxidant glutathione peroxidase 4 was reduced. Greater fibrosis seen 28 These findings suggest Pkm2 ablation primes heart for stress, inflammation, post‐MI. The natural may mitigate reducing highlighting its protective heart.
Language: Английский
Citations
1
International Immunopharmacology, Journal Year: 2025, Volume and Issue: 149, P. 114148 - 114148
Published: Feb. 3, 2025
Language: Английский
Citations
1
Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)
Published: Feb. 21, 2025
Abstract Aims/hypothesis The resolution of apoptotic cells (ACs) is crucial for wound healing and tissue remodeling often impaired by persistent inflammation. This study aimed to elucidate the impact neutrophil extracellular traps (NETs) on diabetic targeting phosphoinositide 3-kinase/Ras-related C3 botulinum toxin substrate 1 (PI3K/Rac1) signaling pathway, which pivotal macrophage efferocytosis. Methods A streptozotocin-induced mouse model was used assess NETs efferocytosis in vivo. effects were evaluated using specific inhibitors agonists PI3K/Rac1 pathway. In vitro, macrophages from wounds or cell lines (Raw264.7) treated with a panel pharmacological agents pathway evaluate Results found inhibit efferocytosis, resulting delayed clearance ACs that accumulate within wounds. Inhibition NET formation mice rescued accompanied reactivation PI3K Rac1 macrophages. Moreover, restored NETs-induced impairment leading rapid healing. Raw264.7 exhibited elevated activation levels when co-cultured vitro. Nevertheless, this inhibited cultured NETs-conditioned medium, attenuated Conclusions/interpretation Targeting emerges as potential therapeutic strategy enhance promoting
Language: Английский
Citations
1
JACC Basic to Translational Science, Journal Year: 2023, Volume and Issue: 8(7), P. 884 - 904
Published: April 26, 2023
Immune cell function among the myocardium, now more than ever, is appreciated to regulate cardiac and pathophysiology. This case for both innate immunity, which includes neutrophils, monocytes, dendritic cells, macrophages, as well adaptive T cells B cells. fueled by cell-intrinsic shifts in metabolism, such glycolysis oxidative phosphorylation, metabolite availability, originates from surrounding extracellular milieu varies during ischemia metabolic syndrome. crosstalk with parenchymal cardiomyocytes fibroblasts, also regulated complex cellular circuits. Although our understanding of immunometabolism has advanced rapidly over past decade, part through valuable insights made cultured there remains much learn about contributions vivo directly within myocardium. Insight into fundamental molecular mechanisms holds potential inform interventions that shift balance maladaptive cardioprotective potentially even regenerative. Herein, we review current working immunometabolism, specifically settings sterile ischemic injury or cardiometabolic disease, contribute onset heart failure. We discuss gaps knowledge this context therapeutic implications.
Language: Английский
Citations
22