Antioxidant and Anti-Inflammatory Functions of High-Density Lipoprotein in Type 1 and Type 2 Diabetes

Antioxidants, Journal Year: 2023, Volume and Issue: 13(1), P. 57 - 57

Published: Dec. 28, 2023

(1) Background: high-density lipoproteins (HDLs) exhibit antioxidant and anti-inflammatory properties that play an important role in preventing the development of atherosclerotic lesions possibly also diabetes. In turn, both type 1 diabetes (T1D) 2 (T2D) are susceptible to having deleterious effects on these HDL functions. The objectives present review expound upon functions HDLs setting cardiovascular diseases discuss contributions onset (2) Methods: this narrative is based literature available from PubMed database. (3) Results: several HDLs, such as paraoxonase-1 activity, compromised T2D, thereby facilitating pro-atherogenic oxidized low-density lipoproteins. addition, diminished ability inhibit pro-inflammatory pathways vessels individuals with T2D. Although less extensive, recent evidence suggests defective antiatherogenic particles T1D. Lastly, substantial indicates a by modulating glucose metabolism. (4) Conclusions perspectives: impaired intriguing targets for mitigating risk Further investigations needed clarify influence glycaemic control nephropathy functionality patients Furthermore, exploring novel antidiabetic drugs used management T2D may provide insights future research.

Language: Английский

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The Role of Polyphenols in Modulating PON1 Activity Regarding Endothelial Dysfunction and Atherosclerosis

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 2962 - 2962

Published: March 4, 2024

The incidence and prevalence of cardiovascular diseases are still rising. principal mechanism that drives them is atherosclerosis, an affection given by dyslipidemia a pro-inflammatory state. Paraoxonase enzymes have protective role due to their ability contribute antioxidant anti-inflammatory pathways, especially paraoxonase 1 (PON1). PON1 binds with HDL (high-density lipoprotein), high serum levels lead state against dyslipidemia, diseases, diabetes, stroke, nonalcoholic fatty liver disease, many others. Modulating expression might be treatment objective significant results in limiting the atherosclerosis. Lifestyle including diet exercise can raise its levels, some beneficial plants been found influence levels; therefore, more studies on herbal components needed. Our purpose highlight roles Praoxonase 1, implications other emphasize modulate expression, targeting potential flavonoids could introduced as supplements our validate hypothesis any effects regarding function.

Language: Английский

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White adipose tissue, a novel antirheumatic target: Clues from its secretory capability and adipectomy‐based therapy

British Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 181(16), P. 2774 - 2793

Published: April 21, 2024

Abstract Background and Purpose White adipose tissue (WAT) is involved in rheumatoid arthritis (RA). This study explored its potential as an antirheumatic target. Experimental Approach WAT status of healthy adjuvant‐induced (AIA) rats were compared. The contribution to RA pathology was evaluated by pre‐adipocyte transplant experiments dissecting perirenal fat pads AIA rats. impact on investigated culturing pre‐adipocytes. Proteins differentially expressed identified the UPLC/MS 2 method. These together with PPARγ siRNA agonist used treat pre‐adipocytes vitro. medium for THP‐1 monocyte culture. Key Results Compared controls, smaller but secreted more leptin, eNAMPT, MCP‐1, TNF‐α, IL‐6. rat increased levels these adipokines recipients. patients' serum induced a similar secretion change impaired differentiation Adipectomy eased AIA‐related immune abnormalities arthritic manifestations. Hepatokines PON1, IGFBP4, GPIHBP1 among differential proteins high blood, inflammatory secretions inhibited expression caused impairment pre‐adipocytes, outcome PPARγ‐silencing. endowed cells ability activate monocytes, which can be abrogated rosiglitazone. Conclusion Implications Certain hepatokines potentiate expedite progression inhibiting PPARγ. Targeting this signalling or abnormal various approaches may reduce severity.

Language: Английский

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Paraoxonase 1: evolution of the enzyme and of its role in protecting against atherosclerosis

Current Opinion in Lipidology, Journal Year: 2024, Volume and Issue: 35(4), P. 171 - 178

Published: June 18, 2024

Purpose of review To the discoveries which led to concept that serum paraoxonase 1 (PON1) is inversely related atherosclerotic cardiovascular disease (ASCVD) incidence, how this association came be regarded as causal and such a role might have evolved. Recent findings Animal models suggest link between PON1 present on HDL atherosclerosis. Serum activity predicts ASCVD with similar reliability cholesterol, but at extremes high low there discordance being potentially more accurate. The gene family has its origins in earliest life forms. Its greatest hydrolytic towards lactones organophosphates, both can generated natural environment. It active wide range substrates thus conservation may resulted from improved survival species facing variety evolutionary challenges. Summary Protection against likely consequence some promiscuous PON1, nonetheless potential for exploitation improve risk prediction prevention ASCVD.

Language: Английский

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Associations between paraoxonase-1 activity and therapeutic drug monitoring indicators in schizophrenia patients treated with olanzapine: A cross-sectional study

Journal of Psychopharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 7, 2025

Objective: Therapeutic drug monitoring (TDM) indicators have been suggested to predict overall outcome responses olanzapine (OLZ) treatments in terms of efficacy and metabolic syndrome. This study aimed investigate whether paraoxonase-1 (PON-1) activity can be used schizophrenia patient outcomes. Methods: Schizophrenic patients ( N = 50) aged between 20 65 years who received OLZ treatment were recruited, their Positive Negative Syndrome Scale scores, PON-1 activity, levels normalized by dose (OLZ/D) its metabolite N-desmethyl-olanzapine (DMO), together with biochemical parameters, determined. Results: OLZ/D significantly correlated 50 (correlation coefficient, r 0.355; p 0.0115). There was also a statistically significant correlation the ratio homocysteine (Hcy) coefficient 0.361; 0.01) negative Hcy triglyceride/high-density lipoprotein (TG/HDL; −0.328; 0.02). Conclusions: as an alternative tool for TDM through measurement metabolite, DMO, identify higher activity. Those show optimal response or lower might greater cardiometabolic risk under long-term treatment. Longitudinal is warranted confirm such observations.

Language: Английский

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Factors involved in human healthy aging: insights from longevity individuals

Frontiers of Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: March 22, 2025

Language: Английский

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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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HDL-Cholesterol and Triglycerides Dynamics: Essential Players in Metabolic Syndrome

Antioxidants, Journal Year: 2025, Volume and Issue: 14(4), P. 434 - 434

Published: April 3, 2025

Metabolic syndrome (MetS) is a complex cluster of interrelated metabolic disorders that significantly elevate the risk cardiovascular disease, making it pressing public health concern worldwide. Among key features MetS, dyslipidemia—characterized by altered levels high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG)—plays crucial role in disorder’s progression. This review aims to elucidate intricate interplay between HDL-C TG within context lipid metabolism health, while also addressing detrimental impact various factors associated comorbidities. The dynamics are explored, highlighting their reciprocal relationship respective contributions pathophysiology MetS. Elevated TGs consistently with reduced concentrations HDL-C, resulting profile promotes development vascular disease. Specifically, as rise, protective effects diminished, leading increased accumulation pro-atherogenic TG-rich lipoproteins low-density particles wall, contributing progression atheromas, which can ultimately result significant ischemic events. Ultimately, this paper underscores significance HDL essential targets for therapeutic intervention, emphasizing potential effectively managing MetS reducing risk.

Language: Английский

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Association of CETP, APOA5, IL6, and PON1 Gene Variants with Dyslipidemia and Cardiovascular Risk in a Population from Cauca Department, Colombia

Genes, Journal Year: 2025, Volume and Issue: 16(5), P. 545 - 545

Published: April 30, 2025

Background: Cardiovascular disease remains the leading cause of death worldwide, and dyslipidemia is a critical, modifiable risk factor. Aim: We sought to evaluate relationship between polymorphisms in CETP (rs3764261), APOA5 (rs662799), IL6 (rs1800796), PON1 (Q192R) lipid parameters, assess their contribution overall cardiovascular an urban cohort from Cauca, Colombia. Methods: In this cross-sectional observational study, 304 participants aged 40–69 years were enrolled. Clinical, anthropometric, biochemical data collected, genotyping was performed for four target polymorphisms. used descriptive statistics characterize sample, non-parametric tests compare levels by genotype, multivariable logistic regression identify independent predictors dyslipidemia. Results: Individuals with exhibited significantly higher total cholesterol VLDL levels, lower HDL elevated Castelli II index compared non-dyslipidemia group. Although genotype frequencies differed groups, only rs662799 variant associated increased suggesting its potential role as genetic biomarker risk. Conclusions: Our findings underscore interplay metabolic factors variants pathogenesis Notably, polymorphism emerged key determinant concentration, highlighting promise personalized stratification management population.

Language: Английский

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The Role of ‘Paraoxonase-1 Activity’ as an Antioxidant in Coronary Artery Diseases

JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH, Journal Year: 2013, Volume and Issue: unknown

Published: Jan. 1, 2013

A majority of the Coronary Artery Diseases (CAD) result from complications atherosclerosis. There is a growing body evidence which has revealed that reduced activity HDL-associated enzyme, paraoxonase1 (PON1), predictive vascular disease in humans, include results prospective studies. The mechanisms by PON1 influences risk continue to be evaluated. It generally thought contributes antioxidant, and thus, antiatherogenic properties High Density Lipoproteins (HDL). Depleted antioxidant levels could factor for coronary artery disease. Hence, this study was done evaluate PON1, as CAD patients.This determine serum 50 controls 60 clinically ECG proven cases compare with total cholesterol triglycerides.Serum (p<0.001) were significantly lower than controls. Serum (p< 0.001) triglyceride higher negative correlation between PON 1 triglycerides. significant (p<0.05).From our present study, we can conclude exert protective effect on HDL preventing its oxidative damage. Further, decreased may CAD, likely explained derangement towards lipid peroxidation. This suggested an important provided protection stress peroxidation CAD. Thus, evaluating effects patients promising treatment prognosis

Language: Английский

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