RESUMEN

Endothelial dysfunction underlies the pathogenesis of many diseases, primarily cardiovascular diseases. Epidemiological studies have shown an inverse dependence between the plasma level of high-density lipoproteins (HDL) and cardiovascular diseases. The results of experimental studies indicate that the antiatherogenic effect of HDL is associated not only with their participation in the reverse transport of excess cholesterol, but also with their regulatory effect on the functions of cells of various organs and tissues, including endothelial cells. The purpose of this review is to consider recent data on the participation of plasma receptors and related intracellular signaling pathways in the mechanism of protective effect of HDL on endothelial cell functions. Understanding the mechanisms of cell function regulation under the influence of HDL is an important step for the development of new ways of pharmacological correction of impaired endothelial functions and creation of effective endothelial protection drugs.

Asunto(s)

Células Endoteliales , Endotelio Vascular , Lipoproteínas HDL , Transducción de Señal , Humanos , Lipoproteínas HDL/metabolismo , Células Endoteliales/metabolismo , Animales , Endotelio Vascular/metabolismo , Enfermedades Cardiovasculares/metabolismo , Receptores de Lipoproteína/metabolismo , Receptores de Lipoproteína/genética

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

Asunto(s)

Apolipoproteína L1 , Apolipoproteína L1/genética , Humanos , Lipoproteínas HDL/genética , Lipoproteínas HDL/sangre , Lipoproteínas HDL/metabolismo , Apolipoproteínas/genética , Animales , Enfermedades Renales/genética , Ratones

RESUMEN

PURPOSE OF REVIEW: Proton nuclear magnetic resonance (NMR) can rapidly assess lipoprotein concentrations and sizes in biological samples. It may be especially useful for quantifying high-density lipoprotein (HDL), which exhibits diverse particle sizes and concentrations. We provide a critical review of the strengths and limitations of NMR for quantifying HDL subclasses. RECENT FINDINGS: Recent studies using NMR have shed light on HDL's role in various disorders, ranging from residual cardiovascular risk to host susceptibility to infection. However, accurately quantifying HDL particle number, size, and concentration (HDL-P) remains a challenge. Discrepancies exist between NMR and other methods such as gel electrophoresis, ion mobility analysis and size-exclusion chromatography in estimating the abundance of HDL species and the ratio of apolipoprotein A-I (APOA1) to HDL particles. SUMMARY: NMR is a low-cost method for quantifying HDL-P that is readily applicable to clinical and translational studies. However, inconsistencies between the results of NMR quantification of HDL-P and other independent methods hinder the interpretation of NMR results. Because proton NMR apparently fails to accurately quantify the sizes and concentrations of HDL, the relevance of such studies to HDL biology poses challenges. This limits our understanding of pathophysiological implications of HDL-P as determined by NMR, particularly in determining cardiovascular disease (CVD) risk.

Asunto(s)

Lipoproteínas HDL , Humanos , Lipoproteínas HDL/sangre , Lipoproteínas HDL/metabolismo , Lipoproteínas HDL/química , Animales , Espectroscopía de Protones por Resonancia Magnética/métodos , Tamaño de la Partícula , Espectroscopía de Resonancia Magnética/métodos

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

Apolipoprotein A-I (apoA-I), the primary protein component of plasma high-density lipoproteins (HDL), is comprised of two structural regions, an N-terminal amphipathic α-helix bundle domain (residues 1-184) and a hydrophobic C-terminal domain (residues 185-243). When a recombinant fusion protein construct [bacterial pelB leader sequence - human apoA-I (1-243)] was expressed in Escherichia coli shaker flask cultures, apoA-I was recovered in the cell lysate. By contrast, when the C-terminal domain was deleted from the construct, large amounts of the truncated protein, apoA-I (1-184), were recovered in the culture medium. Consequently, following pelB leader sequence cleavage in the E. coli periplasmic space, apoA-I (1-184) was secreted from the bacteria. When the pelB-apoA-I (1-184) fusion construct was expressed in a 5 L bioreactor, substantial foam production (~30 L) occurred. Upon foam collection and collapse into a liquid foamate, SDS-PAGE revealed that apoA-I (1-184) was the sole major protein present. Incubation of apoA-I (1-184) with phospholipid vesicles yielded reconstituted HDL (rHDL) particles that were similar in size and cholesterol efflux capacity to those generated with full-length apoA-I. Mass spectrometry analysis confirmed that pelB leader sequence cleavage occurred and that foam fractionation did not result in unwanted protein modifications. The facile nature and scalability of bioreactor-based apolipoprotein foam fractionation provide a novel means to generate a versatile rHDL scaffold protein.

Asunto(s)

Apolipoproteína A-I , Escherichia coli , Proteínas Recombinantes de Fusión , Apolipoproteína A-I/genética , Apolipoproteína A-I/química , Apolipoproteína A-I/metabolismo , Humanos , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/aislamiento & purificación , Lipoproteínas HDL/metabolismo , Lipoproteínas HDL/química , Lipoproteínas HDL/genética

RESUMEN

The association between high-density lipoprotein (HDL) cholesterol and breast cancer (BC) remains controversial due to the high complexity of the HDL particle and its functionality. The HDL proteome was determined in newly diagnosed BC classified according to the molecular type [luminal A or B (LA or LB), HER2, and triple-negative (TN)] and clinical stage of the disease. Women (n = 141) aged between 18 and 80 years with BC, treatment-naïve, and healthy women [n = 103; control group (CT)], matched by age and body mass index, were included. Data-independent acquisition (DIA) proteomics was performed in isolated HDL (D = 1.063-1.21 g/mL). Results: Paraoxonase1, carnosine dipeptidase1, immunoglobulin mMu heavy chain constant region (IGHM), apoA-4, and transthyretin were reduced, and serum amyloid A2 and tetranectin were higher in BC compared to CT. In TNBC, apoA-1, apoA-2, apoC-2, and apoC-4 were reduced compared to LA, LB, and HER2, and apoA-4 compared to LA and HER2. ComplementC3, lambda immunoglobulin2/3, serpin3, IGHM, complement9, alpha2 lysine rich-glycoprotein1, and complement4B were higher in TNBC in comparison to all other types; complement factor B and vitamin D-binding protein were in contrast to LA and HER2, and plasminogen compared to LA and LB. In grouped stages III + IV, tetranectin and alpha2-macroglobulin were reduced, and haptoglobin-related protein; lecithin cholesterol acyltransferase, serum amyloid A1, and IGHM were increased compared to stages I + II. Conclusions: A differential proteomic profile of HDL in BC based on tumor molecular classification and the clinical stage of the disease may contribute to a better understanding of the association of HDL with BC pathophysiology, treatment, and outcomes.

Asunto(s)

Neoplasias de la Mama , Estadificación de Neoplasias , Proteómica , Humanos , Femenino , Proteómica/métodos , Persona de Mediana Edad , Neoplasias de la Mama/sangre , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/clasificación , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Adulto , Anciano , Lipoproteínas HDL/sangre , Lipoproteínas HDL/metabolismo , Anciano de 80 o más Años , Proteoma/metabolismo , Adolescente , Adulto Joven

RESUMEN

Diabetic kidney disease (DKD) is a devastating kidney disease and lacks effective therapeutic interventions. The present study was aimed to determine whether reconstituted high-density lipoprotein (rHDL) ameliorated renal injury in eNOS-/- dbdb mice, a mouse model of DKD. Three groups of mice, wild type C57BLKS/J (non-diabetes), eNOS-/- dbdb (diabetes), and eNOS-/- dbdb treated with rHDL (diabetes+rHDL) with both males and females were used. The rHDL nanoparticles were administered to eNOS-/- dbdb mice at Week 16 at 5 µg/g body weight in ~100 µL of saline solution twice per week for 4 weeks via retroorbital injection. We found that rHDL treatment significantly blunted progression of albuminuria and GFR decline observed in DKD mice. Histological examinations showed that the rHDLs significantly alleviated glomerular injury and renal fibrosis, and inhibited podocyte loss. Western blots and immunohistochemical examinations showed that increased protein abundances of fibronectin and collagen IV in the renal cortex of eNOS-/- dbdb mice were significantly reduced by the rHDLs. Taken together, the present study suggests a renoprotective effect of rHDLs on DKD.

Asunto(s)

Nefropatías Diabéticas , Lipoproteínas HDL , Ratones Endogámicos C57BL , Óxido Nítrico Sintasa de Tipo III , Animales , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/patología , Ratones , Masculino , Óxido Nítrico Sintasa de Tipo III/metabolismo , Lipoproteínas HDL/farmacología , Femenino , Ratones Noqueados , Riñón/patología , Riñón/metabolismo , Riñón/efectos de los fármacos , Albuminuria , Fibronectinas/metabolismo , Fibronectinas/genética , Fibrosis , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/tratamiento farmacológico

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

ABCA1 plays an essential role in the formation of high-density lipoprotein (HDL), and its mutations cause Tangier disease (TD), a familial HDL deficiency. In addition to the disappearance of HDL, TD patients exhibit cholesterol deposition in peripheral tissues through a mechanism poorly understood, which may contribute to the development of premature atherosclerosis. We and others previously showed that ABCA1 deficiency causes hyperactivation of the SREBP2 pathway in vitro. Here, we show using Abca1 knockout mice that ABCA1 deficiency leads to tissue-specific dysregulation of SREBP2 activity in a nutritional status-dependent manner, which may underlie the pathophysiology of TD.

Asunto(s)

Transportador 1 de Casete de Unión a ATP , Transducción de Señal , Enfermedad de Tangier , Animales , Humanos , Ratones , Transportador 1 de Casete de Unión a ATP/genética , Transportador 1 de Casete de Unión a ATP/metabolismo , Transportador 1 de Casete de Unión a ATP/deficiencia , Colesterol/metabolismo , Lipoproteínas HDL/metabolismo , Lipoproteínas HDL/genética , Ratones Endogámicos C57BL , Ratones Noqueados , Especificidad de Órganos , Proteína 2 de Unión a Elementos Reguladores de Esteroles/metabolismo , Proteína 2 de Unión a Elementos Reguladores de Esteroles/genética , Enfermedad de Tangier/genética , Enfermedad de Tangier/metabolismo , Enfermedad de Tangier/patología

RESUMEN

OBJECTIVE: The ratio of myeloperoxidase to high-density lipoprotein (MPO/HDL) has become a novel inflammatory biomarker in the field of cardiovascular disease. MPO and HDL have been reported to be associated with inflammation and lipid metabolism after AIS. However, the effect of MPO/HDL on AIS recurrence has not been studied. We aimed to assess the value of MPO/HDL in predicting relapse 90 days after AIS. METHODS: A total of 363 patients diagnosed with AIS were followed up for 90 days. Patients were assessed for recurrence within 90 days after AIS. Univariate and multivariate analyses were performed to determine the association between MPO/HDL and relapse within 90 days in AIS patients. The receiver operating characteristic curve (ROC) was used to compare the predictive value of MPO, HDL and MPO/HDL for recurrence at 90 days after AIS. RESULTS: The proportion of recurrent stroke patients within 90 days was 6.61% (24/363). Recurrent stroke was associated with NIHSS, WBC, NEUT, UA, DD, Hcy, MPO, HDL, and MPO/HDL. After adjusting for potential confounders, the 90-day recurrence risk of AIS patients increased by 0.03 (P < 0.001) for each unit increase in MPO/HDL. The ROC curve constructed after correcting confounders found that compared with MPO(AUC=0.9698) and HDL(AUC=0.821), MPO/HDL showed the highest AUC value (AUC=0.9801), indicating that MPO/HDL levels had the highest predictive value for 90-day relapse in AIS patients. CONCLUSIONS: MPO and MPO/HDL were independently associated with relapse within 90 days of AIS. MPO/HDL may be an independent predictor of 90-day relapse in AIS patients.

Asunto(s)

Biomarcadores , Accidente Cerebrovascular Isquémico , Lipoproteínas HDL , Peroxidasa , Recurrencia , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Biomarcadores/sangre , Accidente Cerebrovascular Isquémico/sangre , Accidente Cerebrovascular Isquémico/diagnóstico , Lipoproteínas HDL/sangre , Peroxidasa/sangre , Valor Predictivo de las Pruebas , Pronóstico , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo

RESUMEN

BACKGROUND AND AIMS: Inflammatory cells within atherosclerotic lesions secrete proteolytic enzymes that contribute to lesion progression and destabilization, increasing the risk for an acute cardiovascular event. Elastase is a serine protease, secreted by macrophages and neutrophils, that may contribute to the development of unstable plaque. We previously reported interaction of endogenous protease-inhibitor proteins with high-density lipoprotein (HDL), including alpha-1-antitrypsin, an inhibitor of elastase. These findings support a potential role for HDL as a modulator of protease activity. In this study, we test the hypothesis that enhancement of HDL-associated elastase inhibitor activity is protective against atherosclerotic lesion progression. METHODS: We designed an HDL-targeting protease inhibitor (HTPI) that binds to HDL and confers elastase inhibitor activity. Lipoprotein binding and the impact of HTPI on atherosclerosis were examined using mouse models. Histology and immunofluorescence staining of aortic root sections were used to examine the impact of HTPI on lesion morphology and inflammatory features. RESULTS: HTPI is a small (1.6 kDa) peptide with an elastase inhibitor domain, a soluble linker, and an HDL-targeting domain. When incubated with human plasma ex vivo, HTPI predominantly binds to HDL. Intravenous administration of HTPI to mice resulted in its binding to plasma HDL and increased elastase inhibitor activity on isolated HDL. Accumulation of HTPI within plaque was observed after administration to Apoe-/- mice. To examine the effect of HTPI treatment on atherosclerosis, prevention and progression studies were performed using Ldlr-/- mice fed Western diet. In both study designs, HTPI-treated mice had reduced lipid deposition in plaque. CONCLUSIONS: These data support the hypothesis that HDL-associated anti-elastase activity can improve the atheroprotective potential of HDL and highlight the potential utility of HDL enrichment with anti-protease activity as an approach for stabilization of atherosclerotic lesions.

Asunto(s)

Aterosclerosis , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Lipoproteínas HDL , Animales , Aterosclerosis/patología , Aterosclerosis/prevención & control , Aterosclerosis/enzimología , Aterosclerosis/metabolismo , Aterosclerosis/tratamiento farmacológico , Lipoproteínas HDL/metabolismo , Humanos , Ratones Endogámicos C57BL , Ratones , Ratones Noqueados para ApoE , Placa Aterosclerótica , Masculino , Elastasa Pancreática/metabolismo , Aorta/patología , Aorta/efectos de los fármacos , Aorta/enzimología , Aorta/metabolismo , Enfermedades de la Aorta/prevención & control , Enfermedades de la Aorta/patología , Enfermedades de la Aorta/enzimología , Enfermedades de la Aorta/metabolismo , Inhibidores de Proteasas/farmacología , alfa 1-Antitripsina/farmacología , alfa 1-Antitripsina/metabolismo

RESUMEN

Recombinant high-density lipoprotein (rHDL) as anti-atherosclerosis (AS) vehicle has unique advantages including multiple anti-atherogenic functions and homing features to plaques. However, rHDL may be converted into dysfunctional forms due to complex treatment during preparation. Herein, oxidation-induced dysfunction of non-split HDL and rHDL was initially investigated. It was found that although both non-split HDL and rHDL showed oxidative dysfunction behavior, non-split HDL demonstrated superior oxidation defense compared to rHDL due to its intact composition and avoidance of overprocessing such as split and recombination. Unfortunately, in vivo oxidative stress could compromise the functionality of HDL. Therefore, surface engineering of non-split HDL and rHDL with cascade antioxidant enzyme analogues Ebselen and mitochondrial-targeted TPGS-Tempo was conducted to construct a dual-line defense HDL nano system (i.e., T@E-HDLs/rHDL), aiming to restore plaque redox balance and preserving the physiological function of HDL. Results indicated that both T@E-HDLs and rHDLs performed without distinction and exhibited greater resistance to oxidative stress damage as well as better functions than unmodified HDLs in macrophage foam cells. Overall, the modification of dual antioxidants strategy bridges the gap between non-split HDL and rHDL, and provides a promising resolution for the dilemmas of oxidative stress in plaques and HDL self dysfunction.

Asunto(s)

Antioxidantes , Lipoproteínas HDL , Estrés Oxidativo , Proteínas Recombinantes , Estrés Oxidativo/efectos de los fármacos , Lipoproteínas HDL/metabolismo , Lipoproteínas HDL/farmacología , Antioxidantes/farmacología , Proteínas Recombinantes/farmacología , Animales , Humanos , Ratones , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/metabolismo , Oxidación-Reducción/efectos de los fármacos , Isoindoles/farmacología , Compuestos de Organoselenio/farmacología , Compuestos de Organoselenio/química

RESUMEN

Background: The previous findings on the correlation between spirometry and high-density lipoprotein (HDL) cholesterol are intriguing yet conflicting. The aim of this research is to evaluate the relationship between HDL levels and spirometry as well as imaging parameters in patients with chronic obstructive pulmonary disease (COPD) in China. Methods: This study encompasses a total of 907 COPD patients. Participants with complete data from questionnaire interviews, lipid profile examinations, spirometry testing, and computed tomography (CT) scans were included in the analysis. A generalized additive model was employed to identify the non-linear relationship between HDL levels and both spirometry and imaging parameters. In the presence of non-linear correlations, segmented linear regression model was applied to ascertain threshold effects. Results: After adjusting for various factors, we found a non-linear correlation between HDL levels and spirometry/imaging parameters, with an inflection point at 4.2 (66 mg/dL). When Ln (HDL) was below 4.2, each unit increase correlated significantly with reduced post-bronchodilator FEV1 (0.32L, 95% CI: 0.09-0.55), decreased predicted FEV1% (11.0%, 95% CI: 2.7-19.3), and lowered FEV1/FVC (8.0%, 95% CI: 4.0-12.0), along with notable increases in Ln (LAA-950) by 1.20 (95% CI: 0.60-1.79) and Ln (LAA-856) by 0.77 (95% CI: 0.37-1.17). However, no significant associations were observed when Ln (HDL) was greater than or equal to 4.2. Conclusion: A non-linear correlation existed between HDL levels with lung function and CT imaging in COPD patients. Prior to reaching 66 mg/dL, an elevation in HDL was significantly associated with impaired lung function, more severe gas trapping and emphysema.

Asunto(s)

Biomarcadores , Pulmón , Dinámicas no Lineales , Enfermedad Pulmonar Obstructiva Crónica , Espirometría , Tomografía Computarizada por Rayos X , Humanos , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/sangre , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Masculino , Femenino , China/epidemiología , Persona de Mediana Edad , Anciano , Pulmón/fisiopatología , Pulmón/diagnóstico por imagen , Volumen Espiratorio Forzado , Biomarcadores/sangre , HDL-Colesterol/sangre , Valor Predictivo de las Pruebas , Estudios Transversales , Modelos Lineales , Lipoproteínas HDL/sangre , Capacidad Vital

RESUMEN

BACKGROUND: Acute-on-chronic liver failure (ACLF) is characterized by a systemic inflammatory response, predominantly associated with hepatitis B virus in the Asia-Pacific region, with a high short-term mortality rate. The platelet to high-density lipoprotein ratio (PHR) has been used to predict the prognosis of patients with various inflammatory diseases. We aim to is to use the PHR to predict the short-term prognosis of patients with HBV-ACLF. METHOD: In this study, we retrospectively analyzed clinical data from 270 HBV-ACLF patients. Using logistic regression, we identified independent risk factors for short-term mortality and developed a prognostic model. This model was then validated, compared, and its clinical utility assessed via decision curve analysis (DCA). RESULTS: Among the 270 HBV-ACLF patients, 98 patients died within 28 days. The deceased group exhibited a higher proportion of severe hepatic encephalopathy and ascites. Additionally, there was a statistically significant difference (P = 0.046) in the novel inflammation scoring system, PHR, between the two groups. Following stringent variable selection, PHR was identified as a predictive factor for short-term mortality in HBV-ACLF patients using logistic regression analysis (OR: 0.835 (0.756-0.999), P = 0.009), and it exhibited a synergistic effect with certain traditional scores. The prognostic model constructed based on PHR demonstrated a superior ability to predict short-term mortality compared to traditional scores such as Child-Turcotte-Pugh (AUC: 0.889). Evaluation using calibration curves and decision curve analysis (DCA) suggested its practical utility. CONCLUSION: PHR can predict short-term mortality in patients, with a low PHR upon admission being associated with an increased risk of death.

Asunto(s)

Insuficiencia Hepática Crónica Agudizada , Lipoproteínas HDL , Humanos , Masculino , Femenino , Insuficiencia Hepática Crónica Agudizada/mortalidad , Insuficiencia Hepática Crónica Agudizada/sangre , Pronóstico , Persona de Mediana Edad , Estudios Retrospectivos , Adulto , Lipoproteínas HDL/sangre , Plaquetas , Hepatitis B/complicaciones , Hepatitis B/mortalidad , Factores de Riesgo , Recuento de Plaquetas , Virus de la Hepatitis B

RESUMEN

Despite recent findings indicating a paradoxical association between high-density lipoprotein cholesterol (HDL-C) levels and cardiovascular disease (CVD) mortality, the impact of HDL-C on subsequent outcomes after ischemic stroke remains unclear. The study aims to investigate the relationships between HDL-C levels and post-stroke functional outcomes while examining the potential modifying influence of HDL-C-related single nucleotide polymorphisms identified through genome-wide association studies. This cohort study included 1,310 patients diagnosed with acute ischemic stroke (AIS), all of whom had their admission serum lipid profile and genotyping information. Participants were categorized into four groups based on gender and HDL-C level. Prognostic outcomes were assessed using a modified Rankin Scale (mRS) at 1, 3, and 12 months post-admission. Multivariate logistic regression and restricted cubic spline regression analysis were used to assess the associations between HDL-C levels and outcomes. The mean age of patients was 61.17 ± 12.08 years, and 69.31% were men. After adjusting confounders, patients with the highest HDL-C level group had a significantly higher risk of poor functional outcomes at 1, 3, and 12 months following stroke compared to the reference group. Restricted cubic splines depicted a nonlinear association between HDL-C levels and poor prognosis in both men and women. The ABCA1 gene rs2575876 AA genotype combined with abnormal HDL-C levels exhibited a significantly heightened risk of post-stroke adverse outcomes at 1 and 3 months compared to patients with normal HDL-C levels and GG + GA genotype. These findings suggest that the combined effects of ABCA1 genetic variants with either low or high HDL-C levels could further heighten this risk.

Asunto(s)

Transportador 1 de Casete de Unión a ATP , HDL-Colesterol , Accidente Cerebrovascular Isquémico , Polimorfismo de Nucleótido Simple , Humanos , Masculino , Femenino , Persona de Mediana Edad , Accidente Cerebrovascular Isquémico/genética , Accidente Cerebrovascular Isquémico/sangre , Anciano , HDL-Colesterol/sangre , Transportador 1 de Casete de Unión a ATP/genética , Taiwán , Pronóstico , Lipoproteínas HDL/sangre , Lipoproteínas HDL/genética , Factores de Riesgo , Genotipo

RESUMEN

BACKGROUND AND PURPOSE: Genome-wide association studies (GWAS) of metabolic syndrome (MetS) have predominantly focused on non-Asian populations, with limited representation from East Asian cohorts. Moreover, previous GWAS analyses have primarily emphasized the significance of top single nucleotide polymorphisms (SNPs), poorly explaining other SNP signals in linkage disequilibrium. This study aimed to reveal the interaction between rs651821 and rs2266788, the principal variants of apolipoprotein A5 (APOA5), within the most significant loci identified through GWAS on MetS. METHODS: GWAS on MetS and its components was conducted using the data from the Korean Genome and Epidemiology Study (KoGES) city cohort comprising 58,600 individuals with available biochemical, demographic, lifestyle factors, and the most significant APOA5 locus was analyzed further in depth. RESULTS: According to GWAS of MetS and its diagnostic components, a significant association between the APOA5 SNPs rs651821/rs2266788 and MetS/triglycerides/high-density lipoprotein phenotypes was revealed. However, a conditional analysis employing rs651821 unveiled a reversal in the odds ratio for rs2266788. Therefore, rs651821 and rs2266788 emerged as independent and opposing signals in the extended GWAS analysis, i.e., the multilayered effects. Further gene-environment interaction analyses regarding lifestyle factors such as smoking, alcohol consumption, and physical activity underscored these multilayered effects. CONCLUSION: This study unveils the intricate interplay between rs651821 and rs2266788 derived from MetS GWAS. Removing the influence of lead SNP reveals an independent protective signal associated with rs2266788, suggesting a multilayered effect between these SNPs. These findings underline the need for novel perspectives in future MetS GWAS.

Asunto(s)

Apolipoproteína A-V , Estudio de Asociación del Genoma Completo , Síndrome Metabólico , Polimorfismo de Nucleótido Simple , Humanos , Apolipoproteína A-V/genética , Síndrome Metabólico/genética , Masculino , Persona de Mediana Edad , Femenino , República de Corea/epidemiología , Pueblo Asiatico/genética , Predisposición Genética a la Enfermedad , Desequilibrio de Ligamiento , Adulto , Anciano , Triglicéridos/sangre , Lipoproteínas HDL/genética , Pueblos del Este de Asia

RESUMEN

BACKGROUND: The highest mortality and morbidity worldwide is associated with atherosclerotic cardiovascular disease (ASCVD), which has in background both environmental and genetic risk factors. Apolipoprotein L1 (APOL1) variability influences the risk of ASCVD in Africans, but little is known about the APOL1 and ASCVD in other ethnic groups. METHODS: To investigate the role of APOL1 and ASCVD, we have genotyped four (rs13056427, rs136147, rs10854688 and rs9610473) APOL1 polymorphisms in a group of 1541 male patients with acute coronary syndrome (ACS) and 1338 male controls. RESULTS: Individual APOL1 polymorphisms were not associated with traditional CVD risk factors such as smoking, hypertension or diabetes prevalence, with BMI values or plasma lipid levels. Neither individual polymorphisms nor haplotypes were associated with an increased risk of ACS nor did they predict total or cardiovascular mortality over the 10.2 ± 3.9 years of follow-up. CONCLUSIONS: We conclude that APOL1 genetic variability has no major effect on risk of ACS in Caucasians.

Asunto(s)

Síndrome Coronario Agudo , Apolipoproteína L1 , Humanos , Masculino , Apolipoproteína L1/genética , Síndrome Coronario Agudo/genética , Persona de Mediana Edad , República Checa , Anciano , Polimorfismo de Nucleótido Simple , Apolipoproteínas/genética , Lipoproteínas HDL/genética , Factores de Riesgo , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Población Blanca/genética , Haplotipos

RESUMEN

OBJECTIVE: Familial hypercholesterolemia (FH) is characterized by elevated levels of low-density lipoprotein cholesterol (LDL-C) and cardiovascular disease (CVD). Although the role of LDL-C in FH has been studied, the contribution of high-density lipoproteins (HDL) to CVD in FH remains unknown. This study aimed at highlighting the role of HDL in FH. METHODS: HDL-specific phospholipid efflux (HDL-SPE) assay was developed to predict CVD risk. HDL-SPE was examined in FH patients (n=30) and compared with age- and sex-matched non-FH controls (n=60). RESULTS: FH patients had significantly lower HDL-SPE levels (0.90±0.12) than controls (1.12±0.10; p<0.05), despite similar HDL-cholesterol levels in both groups (FH: 57.9±18.7 mg/dl; controls: 57.1±13.8 mg/dl). These differences remained significant after adjusting for confounders. CONCLUSIONS: These findings suggest there may be dysfunctionality of HDL in FH.

Asunto(s)

Hiperlipoproteinemia Tipo II , Lipoproteínas HDL , Fosfolípidos , Humanos , Hiperlipoproteinemia Tipo II/sangre , Hiperlipoproteinemia Tipo II/metabolismo , Masculino , Femenino , Lipoproteínas HDL/metabolismo , Lipoproteínas HDL/sangre , Adulto , Fosfolípidos/metabolismo , Fosfolípidos/sangre , Persona de Mediana Edad , Estudios de Casos y Controles , HDL-Colesterol/sangre , HDL-Colesterol/metabolismo , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/sangre