RESUMEN

Cardiovascular disease (CVD) is the leading cause of mortality globally. Low-density lipoprotein (LDL) plays an important role in CVD pathophysiology. Research has shown the safety and efficacy of keeping LDL at very low levels for CVD prevention. Therefore, experts recommend intense LDL-lowering approaches starting at young ages, promoting the mantras "the lower, the better" and "the earlier, the better." This commentary discusses the challenges regarding applying aggressive LDL-lowering approaches in the general population, including pharmacological efficacy and side effects, the cost-effectiveness of interventions, and patient adherence to treatment regimens.

Asunto(s)

Enfermedades Cardiovasculares , LDL-Colesterol , Lipoproteínas LDL , Prevención Primaria , Humanos , Enfermedades Cardiovasculares/prevención & control , Prevención Primaria/métodos , Lipoproteínas LDL/sangre , LDL-Colesterol/sangre , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Análisis Costo-Beneficio

RESUMEN

Current data suggest that oxidative stress may play an important role in the occurrence of acute central serous chorioretinopathy (CSC), as chorioretinal integrity may be affected by disruption of the patient's metabolic redox balance, indicating the need for biomarkers. In addition to oxidative stress, high-density lipoprotein (HDL) dysfunction due to dyslipidemia can also lead to many types of physical discomfort. However, little is known about the pathophysiology of the disease resulting from oxidative stress and HDL dysfunction in CSC. The aim of this study was to investigate whether serum oxidative stress and HDL functionality markers have an impact on CSC disease. The case series of this study included 33 consecutive patients with treatment-naïve acute CSC. Thirty-five healthy volunteers of similar age were included in this study as non-CSC controls. Serum samples of the participants were taken and routine lipid values, serum Total Antioxidant Status (TAS), Total Oxidant Status (TOS), Oxidized Low Density Lipoprotein (ox-LDL), and Paraoxonase (PON1) levels were measured quantitatively. Serum oxidative stress index (OSI) was then calculated. Serum Ox-LDL, TOS and OSI levels in the acute CSC group, consisting of patients who had never been treated before and had no other disease, were statistically significantly higher than the control group. Conversely, serum PON1 and TAS levels were lower in CSC than in the control group. The relationship between CSC and deterioration in serum redox balance and decrease in PON1 activity, an important marker of HDL functionality, was demonstrated for the first time through this study. According to the literature, serum levels of these biomarkers, which identify acute/chronic inflammation and oxidative stress, have not been measured before in CSC disease. Finally, it is conceivable that redox balance and HDL functionality may be important in the diagnosis and treatment of the acute phase of CSC.

Asunto(s)

Arildialquilfosfatasa , Biomarcadores , Coriorretinopatía Serosa Central , Lipoproteínas LDL , Estrés Oxidativo , Humanos , Coriorretinopatía Serosa Central/sangre , Coriorretinopatía Serosa Central/metabolismo , Masculino , Biomarcadores/sangre , Femenino , Adulto , Arildialquilfosfatasa/sangre , Arildialquilfosfatasa/metabolismo , Persona de Mediana Edad , Lipoproteínas LDL/sangre , Lipoproteínas HDL/sangre , Antioxidantes/metabolismo , Estudios de Casos y Controles

RESUMEN

BACKGROUND: Acute pulmonary embolism (APE) is a major type of venous thromboembolism (VTE) with a high risk of mortality and disability. There is a lack of biomarkers for APE to indicate deteriorating development and predict adverse outcomes. This study evaluated the significance of miR-150-5p in APE aiming to explore a novel potential biomarker for APE. METHODS: The study enrolled APE (n = 137) and deep wein thrombosis (DVT, n = 67) patients and collected plasma samples from all study subjects. The expression of miR-150-5p was analyzed by PCR and its significance in screening APE and pulmonary arterial hypertension (PAH) was assessed by receiver operating curve (ROC) and logistic analyses. The study established oxidized low-density lipoprotein (ox-LDL)-induced human venous endothelial cells (HUVECs). Through cell transfection combined with cell counting kit-8 (CCK8), flow cytometry, and enzyme-linked immunosorbent assay (ELISA), the effect of miR-150-5p on ox-LDL-induced HUVEC injury was evaluated. RESULTS: Significant downregulation of miR-150-5p was observed in the plasma of APE patients compared with DVT patients (P < 0.0001). The plasma miR-150-5p levels in APE patients occurred PAH was much lower than in patients without PAH (P < 0.0001). Reducing miR-150-5p distinguished APE patients from DVT patients (AUC = 0.912) and was identified as a risk factor for the occurrence of PAH in APE patients (OR = 0.385, P = 0.010). In HUVECs, oxidized low-density lipoprotein (ox-LDL) caused inhibited cell proliferation, enhanced apoptosis, increased pro-inflammatory cytokines, reactive oxygen species (ROS), malondialdehyde (MDA), and decreased superoxide dismutase (SOD). Overexpressing miR-150-5p could promote proliferation, inhibit apoptosis, and alleviate inflammation and oxidative stress of ox-LDL-treated HUVECs. CONCLUSIONS: Downregulated plasma miR-150-5p served as a diagnostic biomarker for APE and predicted the predisposition of PAH in APE patients. Overexpressing miR-150-5p could alleviate ox-LDL-induced endothelial cell injury in HUVECs.

Asunto(s)

Biomarcadores , Lipoproteínas LDL , MicroARNs , Embolia Pulmonar , Humanos , Lipoproteínas LDL/sangre , MicroARNs/genética , MicroARNs/sangre , Embolia Pulmonar/genética , Embolia Pulmonar/sangre , Embolia Pulmonar/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Biomarcadores/sangre , Células Endoteliales de la Vena Umbilical Humana , Apoptosis , Hipertensión Arterial Pulmonar/genética , Células Endoteliales/metabolismo , Adulto , Estrés Oxidativo , Anciano

RESUMEN

Despite recent advances, pharmacological treatments of diabetic retinopathy (DR) do not directly address the underlying oxidative stress. This study evaluates the efficacy of a nutraceutical formulation based on maltodextrinated grape pomace extract (MaGPE), an oxidative stress inhibitor, in managing DR. A 6-month, randomized, placebo-controlled clinical trial involving 99 patients with mild to moderate non-proliferative DR was conducted. The MaGPE group showed improvement in best-corrected visual acuity (BCVA) values at T3 (p < 0.001) and T6 (p < 0.01), a reduction in CRT (at T3 and T6, both p < 0.0001) and a stabilization of vascular perfusion percentage, with slight increases at T3 and T6 (+3.0% and +2.7% at T3 and T6, respectively, compared to baseline). Additionally, the levels of reactive oxygen metabolite derivatives (dROMs) decreased from 1100.6 ± 430.1 UCARR at T0 to 974.8 ± 390.2 UCARR at T3 and further to 930.6 ± 310.3 UCARR at T6 (p < 0.05 vs. T0). Similarly, oxidized low-density lipoprotein (oxLDL) levels decreased from 953.9 ± 212.4 µEq/L at T0 to 867.0 ± 209.5 µEq/L at T3 and markedly to 735.0 ± 213.7 µEq/L at T6 (p < 0.0001 vs. T0). These findings suggest that MaGPE supplementation effectively reduces retinal swelling and oxidative stress, contributing to improved visual outcomes in DR patients.

Asunto(s)

Retinopatía Diabética , Suplementos Dietéticos , Estrés Oxidativo , Extractos Vegetales , Polisacáridos , Agudeza Visual , Vitis , Humanos , Retinopatía Diabética/tratamiento farmacológico , Vitis/química , Masculino , Femenino , Extractos Vegetales/farmacología , Persona de Mediana Edad , Agudeza Visual/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Polisacáridos/farmacología , Anciano , Resultado del Tratamiento , Lipoproteínas LDL/sangre , Antioxidantes/farmacología , Especies Reactivas de Oxígeno/metabolismo

RESUMEN

Apolipoprotein E ε4 (APOE4) is a strong genetic risk factor of Alzheimer's disease and metabolic dysfunction. However, whether APOE4 and markers of metabolic dysfunction synergistically impact the deterioration of white matter (WM) integrity in older adults remains unknown. In the UK Biobank data, we conducted a multivariate analysis to investigate the interactions between APOE4 and 249 plasma metabolites (measured using nuclear magnetic resonance spectroscopy) with whole-brain WM integrity (measured by diffusion-weighted magnetic resonance imaging) in a cohort of 1917 older adults (aged 65.0-81.0 years; 52.4 % female). Although no main association was observed between either APOE4 or metabolites with WM integrity (adjusted P > 0.05), significant interactions between APOE4 and metabolites with WM integrity were identified. Among the examined metabolites, higher concentrations of low-density lipoprotein and very low-density lipoprotein were associated with a lower level of WM integrity (b=-0.12, CI=-0.14,-0.10) among APOE4 carriers. Conversely, among non-carriers, they were associated with a higher level of WM integrity (b=0.05, CI=0.04,0.07), demonstrating a significant moderation role of APOE4 (b =-0.18, CI=-0.20,-0.15, P<0.00001).

Asunto(s)

Apolipoproteína E4 , Heterocigoto , Lipoproteínas LDL , Sustancia Blanca , Humanos , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Apolipoproteína E4/genética , Femenino , Masculino , Anciano , Lipoproteínas LDL/sangre , Anciano de 80 o más Años , Estudios de Cohortes , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/patología , Imagen de Difusión por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Factores de Riesgo

RESUMEN

OBJECTIVES: A correlation exists between lipids and osteoporosis (OP), as well as between lipids and rheumatoid arthritis (RA). However, lipids, the relationship between RA and OP is still unclear. This study mainly investigates the relationship between lipid levels and OP risk in RA patients. METHODS: Retrospective collection of RA patient data from July 2017 to May 2022, encompassing baseline demographics, treatment regimens, laboratory results, and bone mineral density (BMD) measurements. Analyses, stratified by BMD subgroups, were conducted using propensity score matching (PSM) based on age, sex, and baseline duration, and binary logistic regression to examine the interplay between lipoprotein levels and other risk factors. The relationship between continuous variables and OP risk was assessed using restricted cubic spline (RCS), followed by a reanalysis of the correlation between varying lipoprotein levels and different factors, segmented according to RCS-determined cutoffs. RESULTS: The study included 2673 RA patients. Binary logistic regression revealed significant associations between high-density lipoprotein (HDL), low-density lipoprotein (LDL), and RA-OP (p < 0.01). Specifically, HDL emerged as a protective factor against OP (OR = 0.40, 95% CI 0.250-0.629; p < 0.001), whereas LDL was identified as a risk factor (OR = 1.56, 95% CI 1.290-1.890; p < 0.001). Furthermore, HDL (RCS cutoff point 1.28 mmol/L) showed a negative, linear correlation with RA-related OP, while LDL (RCS cutoff point 2.63 mmol/L) demonstrated a positive, linear correlation. CONCLUSIONS: The levels of HDL and LDL may be indicators of OP occurrence in RA patients.

Asunto(s)

Artritis Reumatoide , Osteoporosis , Humanos , Artritis Reumatoide/sangre , Artritis Reumatoide/complicaciones , Femenino , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Osteoporosis/sangre , Osteoporosis/etiología , Lipoproteínas LDL/sangre , Anciano , Factores de Riesgo , Lipoproteínas HDL/sangre , Densidad Ósea , Adulto , HDL-Colesterol/sangre

RESUMEN

OBJECTIVES: This study aimed to investigate the effects of a 16-week aerobic exercise program on systolic blood pressure, intracellular cell adhesion molecule-1, vascular cell adhesion molecule-1, and oxidized low-density lipoprotein of obese and nonobese elderly women with isolated systolic hypertension. METHODS: Elderly women aged 70-85 years were recruited and grouped into the normal isolated systolic hypertension ( n  = 12) and obese isolated systolic hypertension groups ( n  = 13). The participants followed an aerobic exercise program, using a wireless heart rate monitor to maintain an appropriate heart rate reserve based on the American College of Sports Medicine exercise guidelines. The two-way repeated measures analysis of variance tested group × time interaction. Pearson's correlation and simple regression assessed the influence of each variable, which showed significant differences. RESULTS: An interaction effect for systolic blood pressure, intracellular cell adhesion molecule-1, and vascular cell adhesion molecule-1 ( P  < 0.05) and a main time effect for oxidized low-density lipoprotein ( P  < 0.05) were observed. A correlation between the rates of change in systolic blood pressure and vascular cell adhesion molecule-1 ( P  < 0.05) with a 42.8% influence ( P  < 0.001) and in intracellular cell adhesion molecule-1 and vascular cell adhesion molecule-1 ( P  < 0.05) with a 21.6% influence ( P  < 0.05) was observed. CONCLUSIONS: These findings collectively showed that the 16-week aerobic exercise program effectively lowered blood pressure in patients with isolated systolic hypertension, particularly in the normal group compared to the obese group. Thus, regular aerobic exercise for 16 weeks or more enhances vascular health, potentially improving the healthy life expectancy of elderly women.

Asunto(s)

Presión Sanguínea , Ejercicio Físico , Hipertensión , Obesidad , Molécula 1 de Adhesión Celular Vascular , Humanos , Femenino , Anciano , Hipertensión/fisiopatología , Ejercicio Físico/fisiología , Obesidad/fisiopatología , Obesidad/complicaciones , Presión Sanguínea/fisiología , Anciano de 80 o más Años , Molécula 1 de Adhesión Celular Vascular/sangre , Inflamación/fisiopatología , Lipoproteínas LDL/sangre , Endotelio Vascular/fisiopatología , Molécula 1 de Adhesión Intercelular/sangre , Hipertensión Sistólica Aislada

RESUMEN

The causal relationship between lipid levels and bladder cancer is still inconclusive currently. We aimed to reveal the causal relationship between triglycerides, HDL, and LDL and the risk of bladder cancer by univariable and multivariable Mendelian randomization (MR) analysis. The single nucleotide polymorphisms (SNPs) of exposure (triglycerides: 441,016 samples; HDL: 403,943 samples; LDL: 440,546 samples) were obtained from UK Biobank. The Genetic variation related to bladder cancer included 1554 cases and 359,640 controls. Univariable and multivariable MR methods were conducted with subsequent analysis, and smoking was regarded as a confounder. The inverse-variance weighted (IVW), MR-Egger, weighted-median method, Cochran's Q test, and MR-PRESSO were considered the main MR analysis and sensitivity analysis methods. Univariable MR analysis results suggested the triglycerides level (P = 0.011, OR = 1.001, 95% CI = 1.000-1.002) was causally associated with increased risk of bladder cancer. Multivariable MR results indicated that higher triglyceride levels could still increase the risk of bladder cancer after adjusting the effects of HDL, LDL, and smoking (P = 0.042, OR = 1.001, 95% CI = 1.000-1.002). Our findings supported that triglyceride level is causally associated with an increased risk of bladder cancer independent of LDL and HDL at the genetic level. Timely attention to changes in blood lipid levels might reduce the risk of bladder cancer.

Asunto(s)

Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Triglicéridos , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/sangre , Triglicéridos/sangre , Factores de Riesgo , Análisis de la Aleatorización Mendeliana , Lipoproteínas LDL/sangre , Lipoproteínas LDL/genética , HDL-Colesterol/sangre , Masculino , Femenino , LDL-Colesterol/sangre , Estudios de Casos y Controles , Lipoproteínas HDL/sangre , Lipoproteínas HDL/genética

RESUMEN

Macrophages in atherosclerotic lesions exhibit a spectrum of behaviours or phenotypes. The phenotypic distribution of monocyte-derived macrophages (MDMs), its correlation with MDM lipid content, and relation to blood lipoprotein densities are not well understood. Of particular interest is the balance between low density lipoproteins (LDL) and high density lipoproteins (HDL), which carry bad and good cholesterol respectively. To address these issues, we have developed a mathematical model for early atherosclerosis in which the MDM population is structured by phenotype and lipid content. The model admits a simpler, closed subsystem whose analysis shows how lesion composition becomes more pathological as the blood density of LDL increases relative to the HDL capacity. We use asymptotic analysis to derive a power-law relationship between MDM phenotype and lipid content at steady-state. This relationship enables us to understand why, for example, lipid-laden MDMs have a more inflammatory phenotype than lipid-poor MDMs when blood LDL lipid density greatly exceeds HDL capacity. We show further that the MDM phenotype distribution always attains a local maximum, while the lipid content distribution may be unimodal, adopt a quasi-uniform profile or decrease monotonically. Pathological lesions exhibit a local maximum in both the phenotype and lipid content MDM distributions, with the maximum at an inflammatory phenotype and near the lipid content capacity respectively. These results illustrate how macrophage heterogeneity arises in early atherosclerosis and provide a framework for future model validation through comparison with single-cell RNA sequencing data.

Asunto(s)

Aterosclerosis , Lipoproteínas HDL , Lipoproteínas LDL , Macrófagos , Conceptos Matemáticos , Fenotipo , Humanos , Macrófagos/metabolismo , Macrófagos/patología , Aterosclerosis/patología , Aterosclerosis/metabolismo , Aterosclerosis/sangre , Lipoproteínas LDL/metabolismo , Lipoproteínas LDL/sangre , Lipoproteínas HDL/sangre , Lipoproteínas HDL/metabolismo , Modelos Cardiovasculares , Metabolismo de los Lípidos , Lipoproteínas/metabolismo , Lipoproteínas/sangre , Simulación por Computador

RESUMEN

Atherosclerosis cardiovascular disease (ASCVD) has become one of the leading death causes in humans. Low-density lipoprotein (LDL) is an important biomarker for assessing ASCVD risk level. Thus, monitoring LDL levels can be an important means for early diagnosis of ASCVD. Herein, a novel electrochemical aptasensor for determination LDL was designed based on nitrogen-doped reduced graphene oxide-hemin-manganese oxide nanoparticles (NrGO-H-Mn3O4 NPs) integrated with clustered regularly interspaced short palindromic repeats and associated proteins (CRISPR/Cas12a) system. NrGO-H-Mn3O4 NPs not only have a large surface area and remarkable enhanced electrical conductivity but also the interconversion of different valence states of iron in hemin can provide an electrical signal. Nonspecific single-stranded DNA (ssDNA) was bound to NrGO-H-Mn3O4 NPs to form a signaling probe and was immobilized on the electrode surface. The CRISPR/Cas12a system has excellent trans-cleavage activity, which can be used to cleave ssDNA, thus detaching the NrGO-H-Mn3O4 NPs from the sensing interface and attenuating the electrical signal. Significant signal change triggered by the target was ultimately obtained, thus achieving sensitive detection of the LDL in range from 0.005 to 1000.0 nM with the detection limit of 0.005 nM. The proposed sensor exhibited good stability, selectivity, and stability and achieved reliable detection of LDL in serum samples, demonstrating its promising application prospects for the diagnostic application of LDL.

Asunto(s)

Aptámeros de Nucleótidos , Técnicas Biosensibles , Sistemas CRISPR-Cas , Técnicas Electroquímicas , Grafito , Hemina , Límite de Detección , Lipoproteínas LDL , Compuestos de Manganeso , Óxidos , Compuestos de Manganeso/química , Lipoproteínas LDL/sangre , Lipoproteínas LDL/química , Humanos , Técnicas Electroquímicas/métodos , Óxidos/química , Grafito/química , Aptámeros de Nucleótidos/química , Hemina/química , Técnicas Biosensibles/métodos , ADN de Cadena Simple/química , Nanopartículas/química

RESUMEN

Inflammation and oxidative stress are both considered to be factors in the etiopathogenesis of schizophrenia. LOX-1 (lectin-like oxidized low-density lipoprotein receptor-1) and ox-LDL (oxidized low-density lipoprotein) have been reported to be active in neuroinflammation pathways in which they are involved in oxidative stress and inflammation. However, its relationship with schizophrenia is unclear. This study aimed to assess the potential connection between serum ox-LDL and LOX-1 levels in schizophrenia patients, their unaffected first-degree relatives, and healthy controls. The study comprised 63 schizophrenia patients, 57 first-degree relatives, and 63 healthy controls who were age, gender, and BMI-matched. Serum ox-LDL and LOX-1 levels were measured. PANSS was used to assess the severity of the disease. Levels of both ox-LDL and LOX-1 were markedly elevated in individuals diagnosed with schizophrenia when compared to both their relatives and a control group. While ox-LDL levels were significantly higher in relatives of patients compared to controls, there was no significant difference between relatives of patients and control groups for LOX-1 levels. Significant correlations were observed between PANNS general and total and ox-LDL levels and PANNS negative and LOX-1 levels. The relationship between ox-LDL and LOX-1 and schizophrenia is quite limited in the literature and is a new field of study. Future studies are needed to evaluate their role in etiopathogenesis.

Asunto(s)

Lipoproteínas LDL , Receptores Depuradores de Clase E , Esquizofrenia , Humanos , Esquizofrenia/sangre , Esquizofrenia/fisiopatología , Lipoproteínas LDL/sangre , Receptores Depuradores de Clase E/sangre , Femenino , Masculino , Adulto , Persona de Mediana Edad , Familia , Adulto Joven

RESUMEN

Atherosclerosis (AS) is the main pathological basis of cardiovascular diseases such as coronary heart disease. Black phosphorus quantum dots (BPQDs) are a novel nanomaterial with good optical properties and biocompatibility, which was applied in the treatment of AS in mice, with good results shown in our previous study. In this study, BPQDs were injected into high-fat diet-fed apolipoprotein E knockout mice as a preventive drug for 12 weeks. Simvastatin, a classic preventive drug for AS, was used as a control to verify the preventive effect of BPQDs. The results showed that after preventive treatment with BPQDs, the plaque area in mice was significantly reduced, the vascular elasticity was increased, and serum lipid levels were significantly lower than those in the model group. To explore the mechanism, macrophages were induced to become foam cells using oxidized low-density lipoprotein. We found that BPQDs treatment could increase cell autophagy, thereby regulating intracellular lipid metabolism. Taken together, these data revealed that BPQDs may serve as a functional drug in preventing the development of AS.

Asunto(s)

Aterosclerosis , Dieta Alta en Grasa , Fósforo , Puntos Cuánticos , Animales , Dieta Alta en Grasa/efectos adversos , Aterosclerosis/prevención & control , Ratones , Fósforo/sangre , Ratones Noqueados , Apolipoproteínas E/genética , Masculino , Autofagia/efectos de los fármacos , Ratones Noqueados para ApoE , Metabolismo de los Lípidos/efectos de los fármacos , Modelos Animales de Enfermedad , Placa Aterosclerótica/prevención & control , Lipoproteínas LDL/metabolismo , Lipoproteínas LDL/sangre , Simvastatina/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Células Espumosas/efectos de los fármacos , Células Espumosas/metabolismo

RESUMEN

BACKGROUND: Vascular oxidative stress and low-grade inflammation are important in the pathology of cardiovascular disorders, including hypertension. Cell culture and animal studies suggest that inorganic dietary nitrate may attenuate oxidative stress and inflammation through nitric oxide (NO), and there is a need to investigate whether this translates to humans. AIM: In this randomised, placebo-controlled crossover study, by measuring a combination of multiple blood biomarkers, we evaluated whether previously reported benefits of dietary nitrate translate to a reduced oxidative stress and an improved inflammation status in 15 men and women (age range: 56-71 years) with treated hypertension. METHODS: We investigated the effects of a single ∼400 mg-dose of nitrate at 3 h post-ingestion (3H POST) and the daily consumption of 2 × âˆ¼400 mg of nitrate over 4 weeks (4WK POST), through nitrate-rich versus nitrate-depleted (placebo) beetroot juice. Measurements included plasma nitrate and nitrite (NOx), oxidised low-density lipoprotein (oxLDL), F2-isoprostanes, protein carbonyls, oxidised (GSSG) and reduced glutathione (GSH); and serum high-sensitive C-reactive protein (hsCRP), chemokines, cytokines, and adhesion molecules. Flow cytometry was used to assess the relative proportion of blood monocyte subsets. RESULTS: At 4WK POST nitrate intervention, the oxLDL/NOx ratio decreased (mainly due to increases in plasma nitrate and nitrite) and the GSH/GSSG ratio (a sensitive biomarker for alterations in the redox status) increased, compared with placebo (for both ratios P < 0.01). The relative proportion of classical (CD14+CD16-) monocytes decreased at 4WK POST for placebo compared to nitrate intervention (P < 0.05). Other oxidative stress and inflammatory markers were not altered by increased nitrate intake relative to placebo. CONCLUSIONS: The data from this study point toward a subtle alteration in the redox balance toward a less pro-oxidative profile by a regular intake of inorganic nitrate from plant foods. CLINICAL TRIAL REGISTRY NUMBER: NCT04584372 (ClinicialTrials.gov).

Asunto(s)

Beta vulgaris , Biomarcadores , Estudios Cruzados , Jugos de Frutas y Vegetales , Hipertensión , Inflamación , Nitratos , Estrés Oxidativo , Humanos , Estrés Oxidativo/efectos de los fármacos , Masculino , Persona de Mediana Edad , Femenino , Anciano , Beta vulgaris/química , Nitratos/sangre , Biomarcadores/sangre , Inflamación/sangre , Inflamación/dietoterapia , Inflamación/tratamiento farmacológico , Hipertensión/dietoterapia , Hipertensión/sangre , Hipertensión/tratamiento farmacológico , Lipoproteínas LDL/sangre , Nitritos/sangre , Proteína C-Reactiva/metabolismo

RESUMEN

Atherosclerotic plaque instability increases the risk of stroke. As such, determining the nature of an instability atherosclerotic plaque may speed up qualification for carotid endarterectomy (CEA), thus reducing the risk of acute vascular events. The aim of the study was to determine the diagnostic value of oxidized LDL cholesterol (ox-LDL), matrix metalloproteinase 9 (MMP-9) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in serum as a prognostic markers of instability atherosclerotic plaques. Serum was collected from 67 patients who underwent CEA in accordance with the qualification criteria. The levels of ox-LDL, MMP-9 and 8-OHdG were assessed by ELISA. The predictive value of the markers was determined based on an ROC curve, and the cut-off points with the highest sensitivity and specificity were determined. Patients with unstable atherosclerotic plaque had significantly higher serum ox-LDL, MMP-9 and 8-OHdG values. It was found that in patients before CEA, ox-LDL >31.4 ng/mL was associated with an 82.5% probability of unstable atherosclerotic plaque, MMP-9 >113.1 ng/mL with 78.6%, and 8-OHdG >2.15 ng/mL with 64.7%. Multivariate regression analysis found ox-LDL to be an independent factor associated with plaque instability. Patients with unstable plaques tend to have higher serum levels of ox-LDL, MMP-9 and 8-OHdG compared to those with stable plaques. The optimal cut-off point for ox-LDL (AUC 0.86, p <0.0001) was 31.14 ng/mL, with 91.18% sensitivity and 78.79% specificity. The high sensitivity and specificity of ox-LDL suggests that it can be used as an independent marker of plaque instability.

Asunto(s)

Biomarcadores , Endarterectomía Carotidea , Lipoproteínas LDL , Metaloproteinasa 9 de la Matriz , Placa Aterosclerótica , Humanos , Lipoproteínas LDL/sangre , Placa Aterosclerótica/cirugía , Placa Aterosclerótica/sangre , Placa Aterosclerótica/patología , Masculino , Femenino , Biomarcadores/sangre , Pronóstico , Metaloproteinasa 9 de la Matriz/sangre , Anciano , Persona de Mediana Edad , Curva ROC , 8-Hidroxi-2'-Desoxicoguanosina/sangre

RESUMEN

The accumulation of excess Low-density lipoprotein (LDL) is strongly associated with the occurrence of heart failure, coronary artery disease and hypercholesterolaemia, and is a major factor in cardiovascular and cerebrovascular disease. Concerns about the ways to decrease LDL level have continuously arisen. In this study, an ionic stimulation-responsive composite (i.e., GO@Apt@SA) is prepared with modification of graphene oxide (GO) utilising LDL-aptamer (Apt) and sodium alginate (SA). The ion-responsive behaviour of GO@Apt@SA synergistically interacts with the specific recognition property of the aptamer, enabling adsorption of LDL with higher capacity and specificity. Under the optimal experimental conditions, the maximum adsorption capacity of GO@Apt@SA for LDL is 730.6 µg mg-1. Interestingly, the aptamer complementary chain could trigger the release of LDL with favourable elution efficiency, which competitively binds with LDL-specific aptamer to trigger LDL release. More importantly, GO@Apt@SA exhibits satisfactory adsorption performances for LDL in goat serum, meaning that the composite material and technology are available for the extraction of LDL from complex sample matrices.

Asunto(s)

Alginatos , Aptámeros de Nucleótidos , Grafito , Lipoproteínas LDL , Grafito/química , Alginatos/química , Lipoproteínas LDL/química , Lipoproteínas LDL/sangre , Aptámeros de Nucleótidos/química , Adsorción , Animales , Cabras

RESUMEN

Dyslipidemia is a major contributor to the development of atherosclerotic cardiovascular disease. Despite high level of physical activity, athletes are not immune from dyslipidemia, but longitudinal data on the variation of lipids are currently lacking. We sought to assess lipid profile changes over time in Olympic athletes practicing different sports disciplines (power, skills, endurance, and mixed). We enrolled 957 consecutive athletes evaluated from London 2012 to Beijing 2022 Olympic Games. Dyslipidemia was defined as low-density lipoprotein (LDL) ≥115 mg/dl, high-density lipoprotein (HDL) <40 mg/dl for males, or HDL <50 mg/dl for females. Hypertriglyceridemia was defined as triglycerides >150 mg/dl. At the follow-up, a variation of ±40 mg/dl for LDL, ±6 mg/dl for HDL, and ±50 mg/dl for triglycerides was considered relevant. Athletes with follow-up <10 months or taking lower lipid agents were excluded. Follow-up was completed in 717 athletes (74.9%), with a mean duration of 55.6 months. Mean age was 27.2 ± 4.8 years old, 54.6% were male (n = 392). Overall, 19.8% (n = 142) athletes were dyslipidemic at both blood tests, being older, practicing nonendurance sports, and predominantly male. In 69.3% (n = 129) of those with elevated LDL at t0, altered values were confirmed at follow-up, while the same occurred in 36.5% (n = 15) with hypo-HDL and 5.3% (n = 1) in those with elevated triglycerides. Weight and fat mass percentage modifications did not affect lipid profile variation. LDL hypercholesterolemia tends to persist over time especially among male, older, and nonendurance athletes. LDL hypercholesterolemia detection in athletes should prompt early preventive intervention to reduce the risk of future development of atherosclerotic disease.

Asunto(s)

Atletas , Dislipidemias , Triglicéridos , Humanos , Masculino , Femenino , Adulto , Triglicéridos/sangre , Adulto Joven , Dislipidemias/sangre , Lípidos/sangre , Estudios Longitudinales , Deportes , Lipoproteínas LDL/sangre

RESUMEN

SUMMARY: Utilizing the Mendelian randomization technique, this research clarifies the putative causal relationship between body mass index (BMI) andbone mineral density (BMD), and the mediating role of low-density lipoprotein (LDL). The implications of these findings present promising opportunities for enhancing our understanding of complex bone-related characteristics and disorders, offering potential directions for treatment and intervention. OBJECTIVE: The objective of this study is to examine the correlation between BMI and BMD, while exploring the intermediary role of LDL in mediating the causal impact of BMI on BMD outcomes via Mendelian randomization. METHODS: In this study, we employed genome-wide association study (GWAS) data on BMI, LDL, and BMD to conduct a comparative analysis using both univariate and multivariate Mendelian randomization. RESULTS: Our study employed a two-sample Mendelian randomization design. Considering BMI as the exposure and BMD as the outcome, our results suggest that BMI may function as a potential protective factor for BMD (ß = 0.05, 95% CI 1.01 to 1.09, P = 0.01). However, when treating LDL as the exposure and BMD as the outcome, our findings indicate LDL as a risk factor for BMD (ß = -0.04, 95% CI 0.92 to 0.99, P = 0.04). In our multivariate Mendelian randomization (MVMR) model, the combined influence of BMI and LDL was used as the exposure for BMD outcomes. The analysis pointed towards a substantial protective effect of LDL on BMD (ß = 0.08, 95% CI 0.85 to 0.97, P = 0.006). In the analysis of mediation effects, LDL was found to mediate the relationship between BMI and BMD, and the effect was calculated at (ß = 0.05, 95% CI 1.052 to 1.048, P = 0.04). CONCLUSION: Our findings suggest that BMI may be considered a protective factor for BMD, while LDL may act as a risk factor. Moreover, LDL appears to play a mediatory role in the causal influence of BMI on BMD.

Asunto(s)

Índice de Masa Corporal , Densidad Ósea , Estudio de Asociación del Genoma Completo , Lipoproteínas LDL , Análisis de la Aleatorización Mendeliana , Humanos , Densidad Ósea/genética , Lipoproteínas LDL/sangre , Polimorfismo de Nucleótido Simple , Femenino

RESUMEN

OBJECTIVE: To explore high density lipoprotein (HDL)/low density lipoprotein (LDL) and total typeⅠcollagen amino terminal extender peptide (t-PINP)/ C-terminal peptide of typeⅠcollagen ß special sequence(ß-CTX)and risk of osteoporosis vertebral fractures (OPVFs) in elderly women. METHODS: The clinical data of 446 female OPVFs patients aged above 60 years old from January 2019 to December 2020 were retrospectively analyzed. According to whether or not fracture, patients were divided into non-fracture group (186 patients) and fracture group(260 patients). Univariate analysis was performed to analysis age, body mass index(BMI), N-terminal mioldle molecular fragment of osteocalcin, N-MID OC), t-PINP, ß-CTX, 25-hydroxyvitamin D[25-(OH) VitD], blood sugar (Glu), total cholesterol(TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), Ca, P, Mg, urea (UREA), creatinine (Cr) and Cystatin C(CysC), and correlation between OPVFs and the above indexes and lipid, bone metabolism indexes between two groups;Logistic regression was performed to analyze risk factors and stratification relationship between vertebral fracture and HDL/LDL, t-PINP/ß-CTX. Logistic regression was used to analyze risk factors and stratification relationship between OPVFs and HDL/LDL, t-PINP/ß-CTX. RESULTS: There were no significant difference in age and BMI between non-fracture group and fracture group (P>0.05). Compared with non-fracture group, contents of HDL, t-PINP/ß-CTX and HDL/LDL in fracture group were decreased, and contents of ß-CTX were increased (P<0.05). OPVFs was positively correlated with ß-CTX (r=0.110, P<0.05), and negatively correlated with HDL, HDL/LDL and t-PINP/ß-CTX (r=-0.157, -0.175, -0.181, P<0.05). HDL and HDL/LDL were negatively correlated with ß-CTX (r=-0.22, -0.12, P<0.05) and t-PINP (r=-0.13, -0.10, P<0.05). 25-(OH) VitD was positively correlated with TC and HDL (r=0.11, 0.18, P<0.05). HDL/LDL was positively correlated with t-PINP/ß-CTX(r=0.11, P=0.02). t-PINP/ß-CTX[OR=0.998, 95%CI(0.997, 1.000), P<0.05], HDL/LDL[OR=0.228, 95%CI(0.104, 0.499), P<0.01] were risk factors for vertebral fracture. The lower levels between two tristratified indicators, the higher the vertebral fracture rate. The risk of fracture was 2.5 and 2 times higher in the lowest stratum than in the highest stratum, with an adjusted OR was[2.112, 95%CI(1.310, 3.404)] and [2.331, 95%CI(1.453, 3.739)], respectively. CONCLUSION: Serum low HDL/LDL and t-PINP /ß-CTX are independent risk factors for OPVF in elderly women, and have good predictive value for OPVF risk.

Asunto(s)

Lipoproteínas LDL , Fracturas Osteoporóticas , Fracturas de la Columna Vertebral , Humanos , Femenino , Anciano , Fracturas Osteoporóticas/sangre , Fracturas de la Columna Vertebral/sangre , Lipoproteínas LDL/sangre , Persona de Mediana Edad , Estudios Retrospectivos , Lipoproteínas HDL/sangre , Procolágeno/sangre , Fragmentos de Péptidos/sangre , Colágeno Tipo I/sangre , Anciano de 80 o más Años , Péptidos/sangre , Osteocalcina/sangre

RESUMEN

Veterans living with HIV (VLWH) and hepatitis C virus (HCV) co-infection have an exacerbated risk of cardiovascular disease (CVD). It is unknown if HCV cure reduces CVD risk in this population. We evaluated changes in low-density lipoprotein (LDL), as a surrogate of CVD risk, 18 months after HCV cure in VLWH. We found significant increases in LDL in VLWH with advanced fibrosis, potentially increasing CVD risk. Lower LDL thresholds to initiate lipid-lowering therapies in VLWH after HCV cure may be warranted.

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Infecciones por VIH , Hepatitis C Crónica , Veteranos , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/complicaciones , Masculino , Persona de Mediana Edad , Femenino , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/complicaciones , Aterosclerosis , Lipoproteínas LDL/sangre , Enfermedades Cardiovasculares , Adulto , Antivirales/uso terapéutico , Coinfección , Medición de Riesgo , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico

RESUMEN

BACKGROUND AND AIMS: Systemic inflammation and oxidation are primary contributors to the development of atherosclerosis. Oxidation of low-density lipoprotein (LDL) particles within the vascular endothelium has been hypothesized to be an initial step in the formation of atherosclerotic plaques, with inflammatory cytokines serving as the signaling mechanism for concomitant macrophage activation. Supplementation with the antioxidative macular xanthophylls (lutein [L], zeaxanthin [Z], and meso-zeaxanthin [MZ]) has been shown to aid in the reduction of inflammatory physiologic responses; therefore, we hypothesized that in our study population, supplementation with these xanthophylls would facilitate a systemic reduction in markers of inflammation and cardiovascular lipid oxidation. METHODS AND RESULTS: In this double-blind placebo-controlled supplementation study, participants were randomly allocated to receive the active intervention containing L (10 mg) + MZ (10 mg) + Z (2 mg) or placebo (containing sunflower oil). Serum concentrations of carotenoids (assessed by HPLC), inflammatory cytokines (IL-6, IL-1ß, TNF-α) and oxidized LDL (OxLDL; by solid-phase sandwich ELISA) were measured at baseline and at 6-months. Results showed that over the supplementation period, compared to placebo, the active group demonstrated statistically significant increases in serum concentrations of L, Z, & MZ (p < 0.05), reductions in inflammatory cytokines IL-1ß (p < 0.001) and TNF-α (p = 0.003), as well as a corresponding reduction in serum OxLDL (p = 0.009). CONCLUSIONS: Our data show that L, Z, & MZ supplementation results in decreased serum IL-1ß, TNF-α, and OxLDL. This suggests that these carotenoids are acting systemically to attenuate oxidative lipid products and inflammation, thus reducing their contribution to atherosclerotic plaque formation.

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Biomarcadores , Citocinas , Suplementos Dietéticos , Lipoproteínas LDL , Luteína , Estrés Oxidativo , Zeaxantinas , Humanos , Zeaxantinas/sangre , Zeaxantinas/administración & dosificación , Masculino , Método Doble Ciego , Femenino , Biomarcadores/sangre , Luteína/sangre , Luteína/administración & dosificación , Lipoproteínas LDL/sangre , Persona de Mediana Edad , Citocinas/sangre , Adulto , Estrés Oxidativo/efectos de los fármacos , Mediadores de Inflamación/sangre , Antioxidantes/administración & dosificación , Inflamación/prevención & control , Inflamación/sangre , Factor de Necrosis Tumoral alfa/sangre , Interleucina-1beta/sangre , Antiinflamatorios/administración & dosificación , Xantófilas/administración & dosificación , Xantófilas/sangre , Anciano , Interleucina-6/sangre , Aterosclerosis/prevención & control , Aterosclerosis/sangre