Vitamin D in atherosclerosis and cardiovascular events

European Heart Journal, Journal Year: 2023, Volume and Issue: 44(23), P. 2078 - 2094

Published: March 21, 2023

Abstract Both experimental and clinical findings linking vitamin D to cardiovascular (CV) risk have prompted consideration of its supplementation improve overall health. Yet several meta-analyses do not provide support for the effectiveness this strategy. Meanwhile, understanding roles in pathophysiology CV diseases has evolved. Specifically, recent work revealed some non-classical pleiotropic effects D, increasing complexity signalling. Within particular microenvironments (e.g. dysfunctional adipose tissue atherosclerotic plaque), can act locally at cellular level through intracrine/autocrine/paracrine feedforward feedback circuits. tissues, ‘local’ levels may influence relevant systemic consequences independently circulating pool. Moreover, links closely other signalling pathways relevance including those driving senescence, ageing, age-related diseases—among them conditions. This review updates knowledge on biology aiming clarify widening gap between evidence. It highlights potential reverse causation confounding correlation status health, need consider novel pathophysiological concepts design future trials that explore atherosclerosis events.

Language: Английский

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Atherosclerosis in diabetes mellitus: novel mechanisms and mechanism-based therapeutic approaches

Nature Reviews Cardiology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 13, 2025

Language: Английский

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The Impact of Modifiable Risk Factors on the Endothelial Cell Methylome and Cardiovascular Disease Development

Frontiers in Bioscience-Landmark, Journal Year: 2025, Volume and Issue: 30(1)

Published: Jan. 7, 2025

Cardiovascular disease (CVD) is the most prevalent cause of mortality and morbidity in Western world. A common underlying hallmark CVD plaque-associated arterial thickening, termed atherosclerosis. Although molecular mechanisms aetiology atherosclerosis remain unknown, it clear that both its development progression are associated with significant changes pattern DNA methylation within vascular cell wall. The endothelium major regulator homeostasis, endothelial dysfunction (ED) considered an early marker for Thus, speculated cells may, part, be causal ED, leading to generally. This review will evaluate extensive evidence environmental risk factors, known atherosclerosis, such as diabetes, metabolic disorder, smoking, hypertension hypercholesterolaemia etc. can affect methylome consequently act alter gene transcription function. Further, potential whereby factors might impact upon activities and/or specificities epigenetic writers erasers which determine [the methyl transferases (DNMTs) Ten Eleven translocases (TETs)] here. Notably, TET proteins members 2-oxoglutarate-dependent dioxygenase superfamily require oxygen (O2) α-ketoglutarate (α-KG) substrates iron-2+ (Fe II) a cofactor. renders their subject modulation by hypoxia, flux cellular redox. significance this, respect modifiable TETs discussed.

Language: Английский

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Deciphering single-cell landscape unravels cell-type-specific functional roles of RNA m⁶A modification in atherosclerosis

Theranostics, Journal Year: 2025, Volume and Issue: 15(10), P. 4785 - 4807

Published: March 29, 2025

Background: Atherosclerosis is a chronic inflammatory disease that the major cause of mortality worldwide. Although several studies have assessed function m6A (N6-methyladenosine) modification in atherosclerosis, its regulatory mechanism at single-cell level remains unclear. This study provides comprehensive atlas regulating cell-type-specific functions atherosclerosis. Methods: We analyzed sequencing data derived from atherosclerosis patients to elucidate influence on diverse cell types. demonstrated potential regulators across various types and key transcription factors involved. Furthermore, we discovered mediated intercellular communication important biological processes. In vitro experiments were conducted further investigate effects ALKBH5, WTAP METTL3 Results: ALKBH5 upregulated endothelial cells induced proliferation migration involved sprouting angiogenesis. smooth muscle cells, upregulation enhanced proliferation, phenotypic transformation. Upregulation YTHDF2 promoted macrophage activation differentiation. identified abnormally activated could regulate manner. Moreover, revealed implicated dysregulated And series experimental validations supported conclusion exert functions. Conclusion: Our provided evidence for roles orchestrating atherosclerotic functions, representing promising targets precision medicine.

Language: Английский

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Epigenetic Mechanisms in Vascular Inflammation: Modulation of Endothelial Adhesion Molecules and Endothelium-Leukocyte Adhesion

Frontiers in Bioscience-Landmark, Journal Year: 2023, Volume and Issue: 28(9)

Published: Sept. 6, 2023

The endothelium, an essential component of the vascular system, plays a critical role in inflammatory response. Under pro-inflammatory stimuli, endothelial cells undergo activation and dysfunction, leading to release mediators upregulation cell adhesion molecules. These changes facilitate adhesion, rolling, transmigration leukocytes into subendothelial space. Emerging evidence suggests that epigenetic mechanisms, including nucleic acid methylation, post-translational histone modifications, non-coding RNA, contribute significantly regulation inflammation expression Understanding molecular signatures govern these processes may provide new insights development therapeutic strategies combat associated diseases. This review aims summarize current knowledge on mechanisms involved modulating intricate underlying inflammation, with specific focus molecules endothelium-leukocyte adhesion.

Language: Английский

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Self-powered photoelectrochemical sensor activated by In2O3/CdTe@ZnS-photoanode coupled with manganese porphyrin-double quenching for methyltransferase detection

Sensors and Actuators B Chemical, Journal Year: 2023, Volume and Issue: 398, P. 134750 - 134750

Published: Oct. 10, 2023

Language: Английский

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High-density lipoprotein mimetic nano-therapeutics targeting monocytes and macrophages for improved cardiovascular care: a comprehensive review

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: May 17, 2024

Abstract The prevalence of cardiovascular diseases continues to be a challenge for global health, necessitating innovative solutions. potential high-density lipoprotein (HDL) mimetic nanotherapeutics in the context disease and intricate mechanisms underlying interactions between monocyte-derived cells HDL showing their impact on inflammation, cellular lipid metabolism, progression atherosclerotic plaque. Preclinical studies have demonstrated that can regulate monocyte recruitment macrophage polarization towards an anti-inflammatory phenotype, suggesting impede atherosclerosis. challenges opportunities associated with clinical application nanotherapeutics, emphasize need additional research gain better understanding precise molecular pathways long-term effects these monocytes macrophages maximize therapeutic efficacy. Furthermore, use nanotechnology treatment highlights nanoparticles targeted treatments. Moreover, concept theranostics combines therapy diagnosis create selective platform conversion traditional medications into specialized customized multifaceted contributions metabolic health via highlight its improve plaque stability avert atherosclerosis-related problems. There is further efficacy develop approaches prevent This review provides comprehensive overview diseases, emphasizing solutions address posed by diseases.

Language: Английский

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DNMT inhibitor, 5-aza-2′-deoxycytidine mitigates di(2-ethylhexyl) phthalate-induced aggravation of psoriasiform inflammation in mice via reduction in global DNA methylation in dermal and peripheral compartments

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 137, P. 112503 - 112503

Published: June 20, 2024

Language: Английский

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Identification of DNA methylation-regulated genes as potential biomarkers for coronary heart disease via machine learning in the Framingham Heart Study

Clinical Epigenetics, Journal Year: 2022, Volume and Issue: 14(1)

Published: Sept. 30, 2022

Abstract Background DNA methylation-regulated genes have been demonstrated as the crucial participants in occurrence of coronary heart disease (CHD). The machine learning based on has tremendous potential for mining non-invasive predictive biomarkers and exploring underlying new mechanisms CHD. Results First, 2085 age-gender-matched individuals Framingham Heart Study (FHS) were randomly divided into training set validation set. We then integrated methylome transcriptome data peripheral blood leukocytes (PBLs) from to probe methylation expression patterns CHD-related genes. A total five hub identified CHD through dimensionality reduction, including ATG7, BACH2, CDKN1B, DHCR24 MPO. Subsequently, features used construct models prediction by LightGBM, XGBoost Random Forest. optimal model established LightGBM exhibited favorable capacity, whose AUC, sensitivity, specificity 0.834, 0.672, 0.864 set, respectively. Furthermore, statuses verified monocytes using microarray sequencing. MPO BACH2 our study population consistent with those PBLs FHS. Conclusions a learning, which may clue epigenetic mechanism

Language: Английский

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The intracellular signaling pathways governing macrophage activation and function in human atherosclerosis

Biochemical Society Transactions, Journal Year: 2022, Volume and Issue: 50(6), P. 1673 - 1682

Published: Nov. 23, 2022

Atherosclerosis is a chronic inflammatory disease characterized by lipid accumulation and plaque formation in arterial vessel walls. Atherosclerotic plaques narrow the lumen to increase risk of heart attacks, ischemic stroke peripheral vascular disease, which are major worldwide health economic burdens. Macrophage within characteristic all stages atherosclerosis their presence potential marker activity stability. Macrophages engulf lipids modified lipoproteins form foam cells that express pro-inflammatory chemotactic effector molecules, stress inducing factors reactive oxygen species. They control stability rupture through secretion metalloproteinases extracellular matrix degradation. Although macrophages can worsen propagating inflammation, they stabilize atherosclerotic tissue remodeling, promoting fibrous cap, clearing apoptotic prevent necrotic core repair. In atherosclerosis, respond dyslipidaemia, cytokines, dying cells, metabolic factors, lipids, physical stimuli epigenetic exhibit heterogeneity activation depending on receive. Understanding these signals pathways driving macrophage function developing established how be pharmacologically modulated, represents strategy for prevention treatment atherosclerosis. This review focusses current understanding controlling Particular attention given intracellular signaling transcription activated biochemical biophysical plaques, integrated regulate

Language: Английский

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