Profile of Lipoprotein Subclasses in Chinese Primary Open-Angle Glaucoma Patients

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(8), P. 4544 - 4544

Published: April 21, 2024

To investigate the plasma lipoprotein subclasses in patients with primary open-angle glaucoma (POAG), a total of 20 Chinese POAG on intraocular pressure (IOP)-lowering treatment and age-matched control subjects were recruited. Based levels cholesterol (TC) low-density (LDL-C), study divided into elevated- normal-level subgroups. The lipoprotein, subclasses, oxidized LDL (oxLDL) quantitatively measured. discrimination potential lipoproteins was evaluated using area under receiver operating characteristic curve (AUC), their correlation clinical parameters also evaluated. Compared to elevated TC and/or LDL-C levels, TC, LDL-C, non-high-density (non-HDL), subclass LDL3 small dense (sdLDL), oxLDL significantly higher levels. No differences any or found between normal Moderate-to-good performance non-HDL, LDL3, sdLDL, discriminating (AUC: 0.710–0.950). Significant negative correlations sdLDL retinal nerve fiber layer (RNFL) thickness superior quadrant average RNFL observed This revealed significant elevation lipoproteins, especially providing insights monitoring specific LDL-C.

Language: Английский

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Computed Tomography Angiography Identified High-Risk Coronary Plaques: From Diagnosis to Prognosis and Future Management

Diagnostics, Journal Year: 2024, Volume and Issue: 14(15), P. 1671 - 1671

Published: Aug. 1, 2024

CT angiography has become, in recent years, a main evaluating modality for patients with coronary artery disease (CAD). Recent advancements the field have allowed us to identity not only presence of obstructive but also characteristics identified lesions. High-risk atherosclerotic plaques are angiographies via number specific and may provide prognostic therapeutic implications, aiming prevent future ischemic events optimizing medical treatment or providing interventions. In light new evidence safety efficacy intervening high-risk plaques, even non-flow-limiting disease, we aim comprehensive review diagnostic algorithms implications plaque vulnerability angiography, identify any differences invasive imaging, analyze factors potential options such patients, as well discuss frontiers, including stenoses role patient stratification.

Language: Английский

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Investigating the pharmacological mechanisms of clopidogrel for carotid stenosis treatment based on network pharmacology and molecular docking techniques

Clinical and Experimental Medicine, Journal Year: 2025, Volume and Issue: 25(1)

Published: March 14, 2025

Carotid artery stenosis is a manifestation of atherosclerosis and associated with an increased risk various cardiovascular diseases. Clopidogrel antiplatelet drug widely used for the prevention treatment atherosclerosis-related This study explores potential molecular mechanisms clopidogrel in carotid through network pharmacology docking techniques. First, methods were to construct target identify its possible 127 action targets. Secondly, gene ontology enrichment analysis indicated that treating closely related inflammatory responses, platelet activation, angiogenesis. The Kyoto Encyclopedia Genes Genomes revealed associations lipid metabolism atherosclerosis. Subsequently, technology was employed screen binding affinity these results exhibited energies less than − 4.20 kcal/mol multiple targets, including TNF, MMP9, PTGS2, CCL2, TLR4, IL-10. indicates has high stable modes thereby exerting anti-inflammatory effects. reveals experimental provide theoretical basis application offer new ideas further development personalized treatment.

Language: Английский

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ApoE [-/-] CA1-overexpressing knock-in mice aggravated atherosclerosis by increasing M1 macrophages

Atherosclerosis Plus, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Carbonic anhydrase I (CA1) has been reported to be a diagnostic and therapeutic target for atherosclerosis (AS). This study aimed verify the essential role of CA1 in AS progression CA1-overexpressing mice. A ApoE [-/-] knock-in mouse model was constructed via CRISPR/Cas9-mediated genome engineering. then induced these transgenic mice administration high-fat diet, second group simultaneously received treatment with methazolamide (MTZ), carbonic inhibitor. Compared without overexpression, had greater average body weight, regardless whether their MTZ or induction status. Sudan IV, hematoxylin eosin Oil Red O staining revealed more plaques fat deposits cardiac aortas than those ordinary ApoE-/- when induced. Moreover, atherogenic index; low-density lipoprotein, total cholesterol triglyceride levels were significantly elevated, high-density lipoprotein declined peripheral blood that mice, animals AS. Immunohistochemistry, Von Kossa fluorescence immunohistochemistry increases expression, calcium deposition M1 macrophages aortic tissues suppressed pathologies above experiments. These findings aggravated suggest aggravates by increasing M1-type macrophages, proinflammatory macrophage subtype.

Language: Английский

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Uptake of ox-LDL by binding to LRP6 mediates oxidative stress-induced BMSCs senescence promoting obesity-related bone loss

Cellular Signalling, Journal Year: 2024, Volume and Issue: 117, P. 111114 - 111114

Published: Feb. 20, 2024

Obesity has long been thought to a main cause of hyperlipidemia. As systemic disease, the impact obesity on organs, tissues and cells are almost all negative. However, relationship between bone loss is most controversial. On one hand, positive effect due increased mechanical loading skeleton, conducive increase mass accommodate extra weight. other obesity-related metabolic oxidative modification low-density lipoprotein (LDL) in vivo caused gradual oxidized LDL (ox-LDL) marrow microenvironment. We had reported that receptor-related protein 6 (LRP6) acts as receptor ox-LDL mediated stromal (BMSCs) uptake ox-LDL. detected elevated serum obese mice. found by LRP6 leaded intracellular reactive oxygen species (ROS) BMSCs, N-acetyl-L-cysteine (NAC) alleviating cellular senescence impairment osteogenesis induced Moreover, co-receptor Wnt signaling. preferentially bound rather dickkopf-related 1 (DKK1), both inhibiting signaling promoting BMSCs senescence. Mesoderm development LRP chaperone (MESD) overexpression inhibition binding LRP6, attenuating stress senescence, eventually rescuing phenotype.

Language: Английский

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Angiopoietin-like Proteins and Lipoprotein Lipase: The Waltz Partners That Govern Triglyceride-Rich Lipoprotein Metabolism? Impact on Atherogenesis, Dietary Interventions, and Emerging Therapies

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(17), P. 5229 - 5229

Published: Sept. 4, 2024

Over 50% of patients who take statins are still at risk developing atherosclerotic cardiovascular disease (ASCVD) and do not achieve their goal LDL-C levels. This residual is largely dependent on triglyceride-rich lipoproteins (TRL) remnants. In essence, remnant cholesterol-rich chylomicron (CM) very-low-density lipoprotein (VLDL) particles play a role in atherogenesis. These remnants increase when lipase (LPL) activity inhibited. ApoCIII has been thoroughly studied as chief inhibitor therapeutic options to curb its effect available. On top apoCIII regulation LPL activity, there more precise control various tissues, which makes it easier physiologically divide the TRL burden according body’s requirements. general, oxidative tissues such skeletal cardiac muscle preferentially up lipids during fasting. Conversely, adipocytes increases significantly after feeding, while decreases concurrently. perspective addresses recent improvements our understanding circadian regulations implications. Three major tissue-specific lipolysis regulators have identified: ANGPTL3, ANGPTL4, ANGPTL8. Briefly, postprandial phase, liver ANGPTL8 acts ANGPTL3 (which released continuously from liver) inhibit heart through an endocrine mechanism. other hand, fasting, by adipocytes, inhibits adipose tissue paracrine manner. inhibitors may treatment hypertriglyceridemia. Several approaches under development. We look forward future studies clarify (a) nature hormonal nutritional factors that determine 4, 8 activities, along with what long-term impacts be expected if impaired pharmacologically; (b) quantitative hierarchy interaction regulatory actions apoCIII, apoAV, ANGPTL activity; (c) strategies for safe proper lipemia; (d) fructose restriction

Language: Английский

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Atherosclerosis, calcific aortic valve disease and mitral annular calcification: Same or different?

International Journal of Cardiology, Journal Year: 2024, Volume and Issue: 420, P. 132741 - 132741

Published: Nov. 16, 2024

Language: Английский

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Efficacy and mechanism of Shenqi Compound in inhibiting diabetic vascular calcification

Molecular Medicine, Journal Year: 2023, Volume and Issue: 29(1)

Published: Dec. 13, 2023

Abstract Background Shenqi Compound (SQC) has been used in clinic for several decades the prevention and treatment of diabetes its complications. But this is merely a heritage experience. The primary aim study to scientifically validate therapeutic effects SQC on diabetic vascular calcification (DVC) an animal model and, simultaneously, uncover potential underlying mechanisms. Method Spontaneous rat- Goto Kakizaki (GK) rats were selected rat modeling. We meticulously designed three distinct groups: control group, group rigorously evaluate influence SQC. Utilizing comprehensive approach that encompassed methods such as pathological staining, western blot analysis, qRT-PCR, RNA sequencing, we thoroughly investigated advantages mechanistic pathways associated with DVC. Result findings from investigation have unveiled extraordinary efficacy significantly mitigating mechanisms driving effect encompass multifaceted facets, including restoration aberrant glucose lipid metabolism, phenotypic transformation smooth muscle cells (VSMCs) into osteogenic-like states, subsequent inhibition cell apoptosis, modulation inflammation responses, remodeling extracellular matrix (ECM), activation Hippo-YAP signaling pathway. Collectively, these lead dissolution deposited calcium salts, ultimately achieving desired Conclusion Our provided compelling robust evidence remarkable reducing This reduction attributed interplay mechanisms, each playing crucial role observed effects. Notably, our illuminate prospective directions further research clinical applications field cardiovascular health. Graphical

Language: Английский

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Plasma lipoprotein(a) is associated with calcification activity of the thoracic aorta and aortic valve in statin naïve individuals with diabetes mellitus

European Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 54(5)

Published: Jan. 24, 2024

Cardiovascular disease (CVD) is a leading cause of death worldwide and rapid progression arterial calcification associated with increased CVD risk.1 18F-Sodium Fluoride Positron Emission Tomography (18F-NaF PET) novel molecular imaging modality for detecting activity, the earliest form calcification, can accurately identify patients who are at risk progressive structures such as thoracic aorta aortic valve.2, 3 Individuals diabetes mellitus have higher burden activity carry disproportionately CVD.4, 5 However, predicting those diabetic individuals will suffer from rapidly difficult, pathophysiology complex, likely influenced by many local systemic mediators. Statin therapies known to modulate calcification.6 Lipoprotein(a) (Lp(a)), an LDL-like particle, characterized presence apolipoprotein(a)(apo(a)) component that covalently linked apoB moiety single disulfide bound, causal factor CVD, principally coronary artery calcific valve stenosis (CAVS), probably through multiple mechanisms, including pro-inflammatory, pro-atherogenic pro-calcification effects.7 relationship between Lp(a) remains incompletely understood. In this study, we aimed determine serum levels structures, determined 18F-NaF PET, in statin naïve mellitus. aged 50–80 type 1 or 2 no prior clinical heart were recruited community 2015 2018 part randomized controlled trial vitamin K colchicine activity; The ViKCoVaC trial.8 All screened CT calcium score, score ≥10 Agatston units included trial. Ten participants zero natural history cohort.3, 8 Briefly, symptomatic disease, planned bypass surgery percutaneous intervention, chronic kidney (eGFR ≤30 mL/min/1.73 m2) using antagonists excluded. full details, detailed inclusion exclusion criteria, been previously published.3, study was approved Royal Perth Hospital Research Ethics committee (REG14-095), registered on www.anzctr.org.au (ACTRN12616000024448) complies declaration Helsinki. provided written informed consent. present cross-sectional analysis, arm not taking therapy (i.e. naïve) time recruitment (n = 46) included. After screening, underwent visit medical medication history. Plasma lipid, lipoprotein, glycated haemoglobin A1c (HbA1c) high sensitivity C-reactive protein (hsCRP) concentrations measured standard methods (Architect c16000 Analyser; Abbott Diagnostics, Laboratories, Park, IL). LDL-cholesterol estimated Friedewald calculation. Total particle concentration undertaken Roche assay (Tina-quant Lipoprotein (a) Gen.2 Cobas pro c503 module). screening cardiac gated (CAC) Philips iCT (128 detector row, 256 slice, 120 kV, 40 mAs) Siemens Definition AS+ (64 128 60mAs) scanner. PET mCT64 PET/CT scanner after intravenous administration 250 MBq h resting period. Pre-treatment beta blocker ivabradine imaging, target rate ≤60.8 Gated scans reconstructed diastolic phase fused scan regions interest drawn around maximum SUV (SUVmax). Ungated attenuation correction aorta. Three adjacent slices centred highest SUVmax averaged result most diseased segment (MDS) SUVmax.8 measures adjusted blood-pool mean SUV, tissue background ratio (TBRmax).8 TBRmax values both established activity.8 For purpose only baseline performed commencement therapies, used. Data analysed Statistical Packages Social Sciences (SPSS, version 29.0, USA). presented ± SD unless otherwise indicated. Skewed variables log-transformed. Associations evaluated Pearson two-tailed correlation linear regression. A variable regression model developed, clinically relevant covariates influence significance defined p-value <.05. Forty-six current analysis (Figure 1). Table describes biochemical characteristics naive They were, average, middle-aged overweight. Two (4%) had noncoronary vascular (87%) subclinical (the nonzero score). prevalence hypertension, overweight (body mass index >25 kg/m2) smoking status (current/ex-smokers) 59%, 91% 35%, respectively. median level 22 nmol/L (7.0–68 nmol/L; 25th–75th percentile); 13% elevated (>125 nmol/L). univariate there statistically significant associations MDS (r 0.390, p .007; Figure 2A) .344, .019; 2B). Serum hsCRP also positively 0.293, .048), but .178, .237). .265, .075) .229, .126). age, male sex (Table 2), independently significantly correlated (β coefficient 0.310; SE 0.035, .030; R2 31.9%) 0.328; 0.047, .029; 25.1%). Replacing hypertension (yes no) independent did alter these (data shown). Our major findings SUVmax. These levels. Previous studies examined association none focus mellitus.9-11 Després et al found TBR compared low levels.9 Zheng reported CAVS.10 another CAVS, Kaiser maximal TBR.11 Discrepancies referred may be due differences subject (established vs. apparent healthy status), protocols use. We extended previous reports examining valve, aorta, majority having atherosclerosis. Whilst meta-analysis ours would worthwhile, it must consider heterogeneity image acquisition protocols, endpoints populations. speculate pathophysiological role promoting different reported.9-11 mechanisms which promote and/or valvular remain unclear. vitro analyses demonstrated cell mineralization, well expression pro-calcific proteins, bone morphogenetic (BMP-2), osteopontin (OPN) runt-related transcription (RUNX2), upregulation pro-inflammatory nuclear factor-κB interleukin-6 (IL-6) expression.12 induce osteogenic differentiation interstitial cells.10 pro-calcifying properties partly relate oxidized phospholipids (OxPLs) carried Lp(a),13, 14 experimental evidence showing effects could alleviated inactivation OxPL.10, 12 complex possibly indirect supported modest strength observed and, despite adjusting confounding variables, represent phenotype inherently susceptible cardiovascular disease. Furthermore, suggests nonspecific inflammation mediator development calcification. effect inflammation, 18F-fluorodexoyglucose (18F-FDG) PET/CT, merits investigation. TBRmax. Unlike SUVmax, corrected blood increase variability quantitative parameters. Hence, sufficiently precise sensitive quantify diminish its Lp(a). speculation further has several limitations. design does allow inferences drawn. our results should viewed hypothesis-generating only. small sample size noteworthy reduce confidence observations. tends II error, therefore, possible underestimated study. Indeed, longitudinal larger sizes needed draw definite conclusions confirm associations. studied relatively range Whether principal apply (such >200 mmol/L) nondiabetic population formally tested. excluded statins analysis. This approach introduce selection bias warrants consideration when interpreting results. all 46 included, biological rationale remove potential addition, excluding users limit translational capacity cohorts, therapy. conclusion, provides new play Recent attempts within territories unsuccessful. Meanwhile, newer antisense inhibition proprotein convertase subtilisin/kexin 9 (PCSK9) apo(a) shown concentrations.15 reduction translates into complications notably demonstration. work funding Foundation (14-095) National Health Medical Council Investigator Grant (APP1194199). During work, Dr Jamie Bellinge Australian Government Training Program Scholarship University Western Australia. Open access publishing facilitated Australia, Wiley & Australia agreement via Librarians. authors conflicts disclose.

Language: Английский

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Research Progress of Vascular Calcification and Vascular Endothelial Growth Factor

Bioprocess, Journal Year: 2024, Volume and Issue: 14(02), P. 48 - 55

Published: Jan. 1, 2024

Language: Английский

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