How Does HDL Participate in Atherogenesis? Antioxidant Activity Versus Role in Reverse Cholesterol Transport

Antioxidants, Journal Year: 2025, Volume and Issue: 14(4), P. 430 - 430

Published: April 2, 2025

Low-density lipoprotein (LDL) chemically modified by reactive oxygen species (ROS), for example, leaking from red blood cells in the vascular compartment, more readily crosses endothelium than does nonoxidatively LDL to enter tissue fluid. Oxidatively (oxLDL) may also be created fluid ROS design, inflammatory white cells, or simply other as a consequence of metabolism. As well oxLDL, glycatively (glycLDL) is formed circulation. High-density (HDL) appears capable decreasing burden lipid peroxides on exposed glucose and its metabolites. The mechanism this that has received most attention antioxidant activity HDL, which due large part presence paraoxonase 1 (PON1). PON1 intimately associated with apolipoprotein A1 component HDL’s domains into cell membranes can transferred. It frequently overlooked hydrolyze substrates, it essential remain virtue hydrophobic amino acid sequences within micellar environment, during isolation serum genetically culture. Otherwise, retain capacity water-soluble such phenyl acetate, whilst failing lipid-soluble molecules. OxLDL probably glycLDL, once they have crossed arterial receptor-mediated transcytosis, are rapidly taken up monocytes process involves scavenger receptors, leading subendothelial foam formation. These precursors atheroma, inducing cross lesion proliferation migration myocytes present wall developing lesion, where transform fibroblasts. atheroma progresses central extracellular lake cholesteryl ester following necrosis apoptosis an overlying fibrous cap continuing grow concentrically around involving oxLDL glycLDL. Within wall, additional generated secreted leakage generally when couplet reduced. important HDL opposes atherogenesis, provide better avenue inquiry identification vulnerable individuals provision new therapies emerged emphasis placed role RCT.

Language: Английский

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Early real-world outcomes of intravitreal aflibercept 8 mg in treatment-Naïve neovascular AMD: AI-assisted fluid volume analysis

International Journal of Retina and Vitreous, Journal Year: 2025, Volume and Issue: 11(1)

Published: April 8, 2025

Abstract Background This study was conducted as a retrospective, exploratory analysis to assess early anatomical and functional effects of intravitreal aflibercept 8 mg in neovascular age-related macular degeneration (nAMD) small cohort patients. Methods retrospective at the Jules Gonin Eye Hospital Lausanne, Switzerland, included treatment-naïve patients with nAMD. Patients received minimum two injections (IVT) over 3-month period. Key outcomes assessed were changes best-corrected visual acuity (BCVA), central subfield thickness (CST), mean retinal (RT), total fluid (TF) volume which calculated sum intraretinal (IRF), subretinal (SRF) pigment epithelial detachment (PED) volumes. These parameters evaluated baseline, month 1, 3 using RetinAI Discovery ® platform, an artificial intelligence-based system. Results 10 eyes enrolled. Mean age 77.7 ± 12.5 years. Comparative between revealed statistically significant reduction CST, RT TF volume, indicating positive response treatment. One adverse event intraocular inflammation (IOI) occurred one patient (10%) after second IVT injection. Treatment subsequently interrupted, IOI resolved topical corticosteroids therapy. Conclusion Intravitreal demonstrated improvements nAMD first 3-months. The use AI-based allowed for detailed automated assessment changes, providing valuable insights into treatment effects. Given design cohort, further studies are warranted long-term potential predictive value on prognosis safety. Clinical trial number Not applicable.

Language: Английский

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Fluid Shear Stress–Regulated Vascular Remodeling: Past, Present, and Future

Arteriosclerosis Thrombosis and Vascular Biology, Journal Year: 2025, Volume and Issue: unknown

Published: April 10, 2025

The vascular system remodels throughout life to ensure adequate perfusion of tissues as they grow, regress, or change metabolic activity. Angiogenesis, the sprouting new blood vessels expand capillary network, versus regression, in which endothelial cells die migrate away remove unneeded capillaries, controls density. In addition, upstream arteries adjust their diameters optimize flow downstream beds, is controlled primarily by sensing fluid shear stress (FSS) from flow. Changes density and small artery tone lead changes resistance bed, leads decreased increased through that feed these vessels. resultant FSS then stimulate inward outward remodeling, respectively. This review summarizes our knowledge FSS–dependent offering insights into potential therapeutic interventions. We first provide a historical overview, discuss concept set point mechanisms low-FSS–mediated high-FSS–mediated remodeling. cover vivo animal models, molecular mechanisms, clinical implications. Understanding underlying physiological FSS–mediated remodeling failure due mutations chronic inflammatory stresses may strategies prevent treat diseases.

Language: Английский

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A Systematic Review of Endothelial Dysfunction in Chronic Venous Disease—Inflammation, Oxidative Stress, and Shear Stress

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3660 - 3660

Published: April 12, 2025

Chronic venous disease (CVD) is among the most common diseases in industrialized countries and has a significant socioeconomic impact. The diversity of clinical symptoms manifestations CVD pose major challenges routine diagnosis treatment. Despite high prevalence huge number surgical interventions performed every day, substantial proportion etiopathogenesis remains unclear. There are several widely advocated generally valid theories “peri-capillary fibrin cuffs” “white cell trapping hypothesis”, which consider role reflux/obstruction, inflammation, vascular remodeling, hemodynamic changes, genetic social risk factors. specific provoking factors for development reflux: incompetence valve system, inflammation wall, hypertension. Over past few years, increasing scientific data demonstrated link between oxidative stress, endothelial dysfunction, inflammation. High levels oxidants persistent can cause cumulative changes hemodynamics, resulting permanent irreversible damage to microcirculation cells. Production reactive oxygen species expression inflammatory cytokines adhesion molecules involved vicious cycle wall remodeling. interaction ROS, particular, superoxide anion radical, with nitric oxide leads decrease NO bioavailability, followed by initiation prolonged vasoconstriction hypoxia impairment tone. This review addresses ED, oxidative, stress mediation. Based on predefined inclusion exclusion criteria, we conducted systematic published articles using PubMed, PMC Europe, Scopus, WoS, MEDLINE, Google Scholar databases interval from 24 April 2002 1 2025. current included studies (n = 197) articles, including new reviews, updates, grey literature, were evaluated according eligibility criteria. selection process was standardized form PRISMA rules, manual search databases, double-check ensure transparent complete reporting reviews. Studies had report quantitative assessments relationship shear chronic disease.

Language: Английский

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Clinical glycoproteomics: methods and diseases

MedComm, Journal Year: 2024, Volume and Issue: 5(10)

Published: Oct. 1, 2024

Abstract Glycoproteins, representing a significant proportion of posttranslational products, play pivotal roles in various biological processes, such as signal transduction and immune response. Abnormal glycosylation may lead to structural functional changes glycoprotein, which is closely related the occurrence development diseases. Consequently, exploring protein can shed light on mechanisms behind disease manifestation pave way for innovative diagnostic therapeutic strategies. Nonetheless, study clinical glycoproteomics fraught with challenges due low abundance intricate structures glycosylation. Recent advancements mass spectrometry‐based have improved our ability identify abnormal glycoproteins samples. In this review, we aim provide comprehensive overview foundational principles recent glycoproteomic methodologies applications. Furthermore, discussed typical characteristics, underlying functions, diseases, brain cardiovascular cancers, kidney metabolic Additionally, highlighted potential avenues future glycoproteomics. These insights provided review will enhance comprehension methods diseases promote elucidation pathogenesis discovery novel biomarkers targets.

Language: Английский

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