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1.
Stem Cell Res Ther ; 15(1): 301, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39278909

RESUMO

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal and rapidly progressive motoneuron degenerative disorder. There are still no drugs capable of slowing disease evolution or improving life quality of ALS patients. Thus, autologous stem cell therapy has emerged as an alternative treatment regime to be investigated in clinical ALS. METHOD: Using Proteomics and Protein-Protein Interaction Network analyses combined with bioinformatics, the possible cellular mechanisms and molecular targets related to mesenchymal stem cells (MSCs, 1 × 106 cells/kg, intrathecally in the lumbar region of the spine) were investigated in cerebrospinal fluid (CSF) of ALS patients who received intrathecal infusions of autologous bone marrow-derived MSCs thirty days after cell therapy. Data are available via ProteomeXchange with identifier PXD053129. RESULTS: Proteomics revealed 220 deregulated proteins in CSF of ALS subjects treated with MSCs compared to CSF collected from the same patients prior to MSCs infusion. Bioinformatics enriched analyses highlighted events of Extracellular matrix and Cell adhesion molecules as well as related key targets APOA1, APOE, APP, C4A, C5, FGA, FGB, FGG and PLG in the CSF of cell treated ALS subjects. CONCLUSIONS: Extracellular matrix and cell adhesion molecules as well as their related highlighted components have emerged as key targets of autologous MSCs in CSF of ALS patients. TRIAL REGISTRATION: Clinicaltrial.gov identifier NCT0291768. Registered 28 September 2016.


Assuntos
Esclerose Lateral Amiotrófica , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Proteômica , Transplante Autólogo , Humanos , Esclerose Lateral Amiotrófica/líquido cefalorraquidiano , Esclerose Lateral Amiotrófica/terapia , Esclerose Lateral Amiotrófica/metabolismo , Células-Tronco Mesenquimais/metabolismo , Proteômica/métodos , Transplante de Células-Tronco Mesenquimais/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Apolipoproteínas E/metabolismo , Apolipoproteínas E/genética , Apolipoproteínas E/líquido cefalorraquidiano , Idoso , Apolipoproteína A-I/líquido cefalorraquidiano , Apolipoproteína A-I/metabolismo , Adulto , Células da Medula Óssea/metabolismo , Mapas de Interação de Proteínas
2.
Narra J ; 4(2): e794, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39280317

RESUMO

Atherosclerosis is a leading cause of cardiovascular disease-related death worldwide. Some studies suggested that the natural ingredients in coffee may negatively affect cardiovascular diseases, while other studies indicated that coffee contains anti-inflammatory compounds that are beneficial for cardiovascular diseases. The aim of this study was to measure the expression of P-selectin in aortic endothelial cells and the level of serum apolipoprotein A-1 (ApoA-1) in an atherosclerosis rat model after the administration of arabica and robusta coffee bean extracts at mild-moderate and high doses. An experimental study was conducted with a complete randomized design using 36 adult male white rats (Rattus norvegicus) divided into six groups: negative control (NC), positive control (PC), arabica mild-moderate dose (A1), arabica high dose (A2), robusta mild-moderate dose (R1), and robusta high dose (R2). Animals were induced atherosclerosis with atherogenic feed and then were treated with arabica and robusta coffee bean extracts at two different doses for four weeks. The results showed that the expression of P-selectin in the group of rats treated with robusta coffee bean extract was lower than arabica coffee bean extract group. Rats with robusta coffee bean extract mild-moderate dose had the highest ApoA-1 levels compared to other groups significantly (p<0.05). The level of ApoA-1 was higher in both mild-moderate and high dose of robusta coffee groups compared to the negative control group (both with p<0.001). In conclusion, mild-moderate intake of robusta coffee bean extract could reduce aortic P-selectin immunoexpression and increase serum ApoA-1 levels in an atherosclerosis rat model.


Assuntos
Aorta , Apolipoproteína A-I , Aterosclerose , Coffea , Modelos Animais de Doenças , Selectina-P , Extratos Vegetais , Animais , Selectina-P/sangue , Selectina-P/metabolismo , Aterosclerose/sangue , Aterosclerose/tratamento farmacológico , Masculino , Ratos , Coffea/química , Extratos Vegetais/farmacologia , Extratos Vegetais/administração & dosagem , Apolipoproteína A-I/sangue , Aorta/metabolismo , Aorta/efeitos dos fármacos
3.
Biochim Biophys Acta Biomembr ; 1866(7): 184375, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39128552

RESUMO

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.


Assuntos
Apolipoproteína A-I , Escherichia coli , Proteínas Recombinantes de Fusão , Apolipoproteína A-I/genética , Apolipoproteína A-I/química , Apolipoproteína A-I/metabolismo , Humanos , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação , Lipoproteínas HDL/metabolismo , Lipoproteínas HDL/química , Lipoproteínas HDL/genética
4.
Obes Surg ; 34(9): 3401-3411, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39141186

RESUMO

INTRODUCTION: Obesity, a major global health concern, is a known risk factor for cardiovascular disease (CVD), often due to dyslipidemia and insulin resistance. Laparoscopic sleeve gastrectomy (LSG) is an effective weight reduction surgery that not only alters body metabolism and gastrointestinal physiology but also significantly lowers cardiovascular disease risk. METHODS: This study explores the impact of weight loss on serum high-sensitivity C-reactive protein (hs-CRP), an established inflammatory marker, and changes in cardiovascular risk factors, particularly high-density lipoprotein-cholesterol (HDL-C) ratios, serum apo A-1, lipid profile, and HOMA-IR in severe obesity undergoing LSG. Anthropometric measurements and blood samples were collected preoperatively and 6 months postoperatively to hs-CRP, HOMA-IR, lipid profile, apo A-1, and low- and high-density lipoprotein-cholesterol (LDL-C/HDL-C) ratios, total cholesterol to HDL-C (TC/HDL-C) ratio, and monocyte to high-density lipoprotein-cholesterol ratio (MHR). RESULTS: In total, 70 patients were analyzed after 6 months and reached %TWL 27.4 ± 9.5 and %EWL 62.0 ± 15.4. Significant improvements were noted in all measured biomarkers. Analysis showed that each unit reduction in BMI significantly affected hs-CRP and HDL-C. Furthermore, moderate associations between hs-CRP and various cardiovascular disease risk biomarkers, including a negative correlation with apo A-1 and positive correlations with total cholesterol (TC), TC/HDL-C, and LDL-C/HDL-C, along with a mild positive correlation with HOMA-IR. CONCLUSION: Weight loss following LSG significantly reduced inflammation and improved atheroprotection. Improved inflammation markers were associated with favorable changes in cardiovascular risk factors, including HDL-C ratios particularly TC/HDL-C, LDL-C/HDL-C, and apo A-1.


Assuntos
Apolipoproteína A-I , Proteína C-Reativa , Doenças Cardiovasculares , HDL-Colesterol , Gastrectomia , Fatores de Risco de Doenças Cardíacas , Laparoscopia , Obesidade Mórbida , Redução de Peso , Humanos , Masculino , Feminino , Apolipoproteína A-I/sangue , Redução de Peso/fisiologia , Proteína C-Reativa/metabolismo , Proteína C-Reativa/análise , Obesidade Mórbida/cirurgia , Obesidade Mórbida/sangue , Adulto , HDL-Colesterol/sangue , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Gastrectomia/métodos , Pessoa de Meia-Idade , Biomarcadores/sangue , Fatores de Risco , Resistência à Insulina
5.
BMC Pediatr ; 24(1): 493, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39095736

RESUMO

BACKGROUND: Type 1 diabetes mellitus (T1DM) is characterized by immune and metabolic dysregulation. Apo1/Fas is implicated in maintaining homeostasis of the immune system. Cytokeratin-18 (cCK-18) is a predictive marker of liver disorders in T2DM. Intercellular adhesion molecule-1 (ICAM-1) is considered to increase susceptibility to diabetes mellitus. All three markers are associated with endothelial function, apoptosis and diabetes-related complications. The possible role of Apo1/Fas, cCK-18 and ICAM-1 was investigated in children and adolescents with T1DM. METHOD: Forty-nine (49) children and adolescents with T1DM and 49 controls were included in the study. Somatometric measurements were obtained and the Body Mass Index (BMI) of the participants was calculated. Biochemical parameters were measured by standard laboratory methods and Apo1/Fas, cCK-18 and ICAM-1 were measured using appropriate ELISA kits. The statistical analysis was performed using the IBM SPSS Statistics 23 program. RESULTS: Apo1/Fas (p = 0.001), cCK-18 (p < 0.001) and ICAM-1 (p < 0.001) were higher in patients with T1DM compared to the controls. Apo1Fas was negatively correlated with glucose (p = 0.042), uric acid (p = 0.026), creatinine (p = 0.022), total cholesterol (p = 0.023) and LDL (p = 0.005) in the controls. In children and adolescents with T1DM, Apo1/Fas was positively correlated with total cholesterol (p = 0.013) and LDL (p = 0.003). ICAM-1 was negatively correlated with creatinine (p = 0.019) in the controls, whereas in patients with T1DM it was negatively correlated with HbA1c (p = 0.05). CONCLUSIONS: Apo1/Fas, cCK-18 and ICAM-1 may be useful as serological markers for immune and metabolic dysregulation in children and adolescents with T1DM. Also, Apo1/Fas may have a protective role against metabolic complications in healthy children.


Assuntos
Biomarcadores , Diabetes Mellitus Tipo 1 , Molécula 1 de Adesão Intercelular , Humanos , Diabetes Mellitus Tipo 1/sangue , Molécula 1 de Adesão Intercelular/sangue , Criança , Adolescente , Masculino , Feminino , Biomarcadores/sangue , Estudos de Casos e Controles , Queratina-18/sangue , Receptor fas/sangue , Apoptose , Apolipoproteína A-I/sangue
6.
J Am Heart Assoc ; 13(14): e034763, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38958152

RESUMO

BACKGROUND: The cholesterol efflux capacity of high density lipoprotein (HDL) is negatively associated with cardiovascular risk. Small HDL particles account almost quantitatively for cholesterol efflux capacity, perhaps mediated through efflux of cholesterol and outer leaflet plasma membrane phospholipids by ABCA1 (ATP binding cassette subfamily A member 1). People with type 1 diabetes are at increased coronary artery disease (CAD) risk despite normal HDL-cholesterol concentrations. We therefore tested the hypothesis that small HDL particles (HDL-P)-rather than HDL-cholesterol-predict incident CAD in type 1 diabetes. METHODS AND RESULTS: Incident CAD (CAD death, myocardial infarction, or coronary revascularization) was determined in 550 individuals with childhood-onset type 1 diabetes. HDL-P was quantified by calibrated ion mobility analysis and cholesterol efflux capacity was quantified with validated assays. During a median follow-up of 26 years, 36.5% of the participants developed incident CAD, for an incidence density of 181.3 per 10 000 person-years. In multivariable Cox models, neither HDL-cholesterol nor apolipoprotein A1 concentration was significantly associated with CAD risk. In contrast, higher extra-small HDL-P concentrations were significantly associated with decreased CAD risk (hazard ratio [HR], 0.26 [95% CI, 0.14-0.50]). Weaker associations were observed for total HDL-P (HR, 0.88 [95% CI, 0.83-0.93]), small HDL (HR, 0.83 [95% CI, 0.68-1.02]), medium HDL (HR, 0.79 [95% CI, 0.71-0.89]), and large HDL (HR, 0.72 [95% CI, 0.59-0.89]). Although cholesterol efflux capacity was negatively associated with incident CAD, this association was no longer significant after adjustment for total HDL-P. CONCLUSIONS: Lower concentrations of total HDL-P and HDL subpopulations were positively associated with incident CAD independently of HDL-cholesterol, apolipoprotein A1, and other common CVD risk factors. Extra-small HDL was a much stronger predictor of risk than the other HDLs. Our data are consistent with the proposal that extra-small HDL plays a critical role in cardioprotection in type 1 diabetes, mediated by macrophage cholesterol efflux by the ABCA1 pathway.


Assuntos
HDL-Colesterol , Doença da Artéria Coronariana , Diabetes Mellitus Tipo 1 , Tamanho da Partícula , Humanos , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/diagnóstico , Masculino , Feminino , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico , Incidência , Adulto , HDL-Colesterol/sangue , Biomarcadores/sangue , Lipoproteínas HDL/sangue , Apolipoproteína A-I/sangue , Pessoa de Meia-Idade , Fatores de Risco , Medição de Risco/métodos , Modelos de Riscos Proporcionais , Fatores de Tempo
7.
Nutr Metab Cardiovasc Dis ; 34(10): 2353-2359, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39003129

RESUMO

BACKGROUND AND AIMS: Correction of calcium and protein undernutrition using milk, yoghurt, and cheese in older adults in aged care homes is associated with reduced fractures and falls. However, these foods contain potentially atherogenic fats. We aimed to determine whether this intervention that increased dairy consumption to recommended levels adversely affects serum lipid profiles. METHOD AND RESULTS: This was a sub-group analysis of a 2-year cluster-randomised trial involving 60 aged care homes in Australia. Thirty intervention homes provided additional milk, yoghurt, and cheese on menus while 30 control homes continued with their usual menus. A sample of 159 intervention and 86 controls residents (69% female, median age 87.8 years) had dietary intakes recorded using plate waste analysis and fasting serum lipids measured at baseline and 12 months. Diagnosis of cardiovascular disease and use of relevant medications were determined from medical records. Outcome measures were serum total, HDL and LDL cholesterol and ApoA-1 & B. Intervention increased daily dairy servings from 1.9 ± 1.0 to 3.5 ± 1.4 (p < 0.001) while controls continued daily intakes of ≤2 servings daily (1.7 ± 1.0 to 2.0 ± 1.0 (p = 0.028). No group differences were observed for serum total cholesterol/high-density lipoprotein-C (TC/HDL-C) ratio, Apoprotein B/Apoprotein A-1 (ApoB/ApoA-1) ratio, low-density lipoprotein-C (LDL-C), non-HDL-C, or triglycerides (TGs) at 12 months. CONCLUSION: Among older adults in aged care homes, correcting insufficiency in intakes of calcium and protein using milk, yoghurt and cheese does not alter serum lipid levels, suggesting that this is a suitable intervention for reducing the risk of falls and fractures. CLINICAL TRIAL REGISTRY: Australian New Zealand Clinical Trials Registry (ACTRN12613000228785) 2012; https://www.anzctr.org.au.


Assuntos
Biomarcadores , Laticínios , Valor Nutritivo , Recomendações Nutricionais , Humanos , Feminino , Masculino , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Austrália , Fatores de Tempo , Instituição de Longa Permanência para Idosos , Idoso , Lipídeos/sangue , Fatores Etários , Estado Nutricional , Apolipoproteína A-I/sangue , Casas de Saúde , Dieta Saudável , Iogurte , Fatores de Risco , HDL-Colesterol/sangue , Queijo , LDL-Colesterol/sangue
8.
Front Immunol ; 15: 1417270, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39040119

RESUMO

Apolipoprotein A-I(ApoA-I) is a member of blood apolipoproteins, it is the main component of High density lipoprotein(HDL). ApoA-I undergoes a series of complex processes from its generation to its composition as spherical HDL. It not only has a cholesterol reversal transport function, but also has a function in modulating the inflammatory response. ApoA-I exerts its anti-inflammatory effects mainly by regulating the functions of immune cells, such as monocytes/macrophages, dendritic cells, neutrophils, and T lymphocytes. It also modulates the function of vascular endothelial cells and adipocytes. Additionally, ApoA-I directly exerts anti-inflammatory effects against pathogenic microorganisms or their products. Intensive research on ApoA-I will hopefully lead to better diagnosis and treatment of inflammatory diseases.


Assuntos
Apolipoproteína A-I , Inflamação , Humanos , Apolipoproteína A-I/metabolismo , Apolipoproteína A-I/imunologia , Animais , Inflamação/imunologia , Inflamação/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Lipoproteínas HDL/metabolismo
9.
Respir Res ; 25(1): 285, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39026259

RESUMO

BACKGROUND: Dysregulation of lipid metabolism is implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). However, the association between the blood lipid profiles and the prognosis of IPF is not well defined. We aimed to identify the impacts of lipid profiles on prognosis in patients with IPF. METHODS: Clinical data of 371 patients with IPF (145 and 226 in the derivation and validation cohorts, respectively), including serum lipid profiles (total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein A-I [Apo A-I], and apolipoprotein B), were retrospectively collected. The association with mortality was analyzed using the Cox proportional hazard model. RESULTS: In the derivation cohort, the mean age was 67.5 years, 86.2% were men, and 30.3% died during the follow-up (median: 18.0 months). Non-survivors showed lower lung function and greater gender-age-physiology scores than survivors. Among the serum lipid profiles, the levels of triglyceride and Apo A-I were significantly lower in non-survivors than in survivors. In the multivariate Cox analysis, low Apo A-I levels (< 140 mg/dL) were independently associated with the risk of mortality (hazard ratio 3.910, 95% confidence interval 1.170-13.069; P = 0.027), when adjusted for smoking history, body mass index, GAP score, and antifibrotic agent use. In both derivation and validation cohorts, patients with low Apo A-I levels (< 140 mg/dL) had worse survival (median survival: [derivation] 34.0 months vs. not reached, P = 0.003; [validation] 40.0 vs. 53.0 months, P = 0.027) than those with high Apo A-I levels in the Kaplan-Meier survival analysis. CONCLUSIONS: Our results indicate that low serum Apo A-1 levels are an independent predictor of mortality in patients with IPF, suggesting the utility of serum Apo A-I as a prognostic biomarker in IPF.


Assuntos
Biomarcadores , Fibrose Pulmonar Idiopática , Lipídeos , Humanos , Fibrose Pulmonar Idiopática/sangue , Fibrose Pulmonar Idiopática/diagnóstico , Fibrose Pulmonar Idiopática/mortalidade , Masculino , Feminino , Idoso , Biomarcadores/sangue , Prognóstico , Estudos Retrospectivos , Pessoa de Meia-Idade , Lipídeos/sangue , Estudos de Coortes , Apolipoproteína A-I/sangue , Seguimentos
10.
Lipids Health Dis ; 23(1): 220, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39039525

RESUMO

BACKGROUND: Proprotein convertase subtilisins/kexin 6 (PCSK6) polymorphisms have been shown to be associated with atherosclerosis progression. This research aimed to evaluate the relationship of PCSK6 rs1531817 polymorphisms with coronary stenosis and the prognosis in premature myocardial infarction (PMI) patients. METHODS: This prospective cohort analysis consecutively included 605 PMI patients who performed emergency percutaneous coronary intervention (PCI) at Tianjin Chest Hospital sequentially between January 2017 and August 2022, with major adverse cardiovascular events (MACEs) as the outcome. Analyses assessed the relationships among PCSK6 rs1531817 polymorphism, Gensini score (GS), triple vessel disease (TVD), and MACEs. RESULTS: 92 (16.8%) patients experienced MACEs with an average follow-up of 25.7 months. Logistic analysis revealed that the PCSK6 rs1531817 CA + AA genotype was an independent protective factor against high GS and TVD. Cox analysis revealed that the PCSK6 rs1531817 CA + AA genotype was an independent protective factor against MACEs. The mediation effect results showed that apolipoprotein A1/apolipoprotein B (ApoA1/ApoB) partially mediated the association between PCSK6 rs1531817 polymorphism and coronary stenosis and that total cholesterol/high-density lipoprotein (TC/HDL) and TVD partially and in parallel mediated the association between the PCSK6 rs1531817 polymorphism and MACEs. CONCLUSION: Patients with the PCSK6 CA + AA genotype have milder coronary stenosis and a better long-term prognosis; according to the mediation model, ApoA1/ApoB and TC/HDL partially mediate. These results may provide a new perspective on clinical therapeutic strategy for anti-atherosclerosis and improved prognosis in PMI patients.


Assuntos
Estenose Coronária , Infarto do Miocárdio , Polimorfismo de Nucleotídeo Único , Humanos , Feminino , Masculino , Estudos Prospectivos , Infarto do Miocárdio/genética , Pessoa de Meia-Idade , Prognóstico , Estenose Coronária/genética , Adulto , Apolipoproteína A-I/genética , Intervenção Coronária Percutânea , Serina Endopeptidases/genética , Genótipo , Apolipoproteína B-100/genética , Predisposição Genética para Doença
11.
BMC Endocr Disord ; 24(1): 110, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38987727

RESUMO

BACKGROUND: The high-density lipoprotein cholesterol to apolipoprotein A-I index (HDL-C/ApoA-I) may be practical and useful in clinical practice as a marker of atherosclerosis. This study aimed to investigate the association between the HDL-C/ApoA-I index with cardiometabolic risk factors and subclinical atherosclerosis. METHODS: In this cross-sectional sub-analysis of the GEA study, 1,363 individuals, women (51.3%) and men (48.7%) between 20 and 75 years old, without coronary heart disease or diabetes mellitus were included. We defined an adverse cardiometabolic profile as excess adipose tissue metrics, non-alcoholic liver fat measured by non-contrasted tomography, metabolic syndrome, dyslipidemias, and insulin resistance. The population was stratified by quartiles of the HDL-C/Apo-AI index, and its dose-relationship associations were analysed using Tobit regression, binomial, and multinomial logistic regression analysis. RESULTS: Body mass index, visceral and pericardial fat, metabolic syndrome, fatty liver, high blood pressure, and CAC were inversely associated with the HDL-C/ApoA-I index. The CAC > 0 prevalence was higher in quartile 1 (29.2%) than in the last quartile (22%) of HDL-C/ApoA-I index (p = 0.035). The probability of having CAC > 0 was higher when the HDL-C/ApoA-I index was less than 0.28 (p < 0.001). This association was independent of classical coronary risk factors, visceral and pericardial fat measurements. CONCLUSION: The HDL-C/ApoA-I index is inversely associated with an adverse cardiometabolic profile and CAC score, making it a potentially useful and practical biomarker of coronary atherosclerosis. Overall, these findings suggest that the HDL-C/ApoA-I index could be useful for evaluating the probability of having higher cardiometabolic risk factors and subclinical atherosclerosis in adults without CAD.


Assuntos
Apolipoproteína A-I , Fatores de Risco Cardiometabólico , HDL-Colesterol , Doença da Artéria Coronariana , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Transversais , Apolipoproteína A-I/sangue , HDL-Colesterol/sangue , Adulto , Idoso , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/sangue , Aterosclerose/epidemiologia , Aterosclerose/diagnóstico , Síndrome Metabólica/epidemiologia , Adulto Jovem , Biomarcadores/análise , Biomarcadores/sangue , Fatores de Risco , Vasos Coronários/patologia , Vasos Coronários/diagnóstico por imagem
12.
J Proteome Res ; 23(8): 3515-3523, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39007742

RESUMO

Acute phase protein (APP) response to vaccine challenges is an attractive alternative to natural infection for identifying pigs with increased disease resilience and monitoring the productive performance. Currently, the methods used for APP quantification are diverse and often based on techniques that use antibodies that are not necessarily pig specific. The objective of this work is the development of a method based on a UPLC-SRM/MS system for simultaneous determination of haptoglobin, apolipoprotein A1, C-reactive protein, pig-major acute protein, and serum amyloid A and its application in pigs to monitor the effect of a vaccine administered against porcine reproductive and respiratory syndrome virus (PRRSV). With the aim of tracing the complete analytical process for each proteotypic peptide, a synthetic QconCat polypeptide construct was designed. It was possible to develop an SRM method including haptoglobin, apolipoprotein A1, pig-MAP, and serum amyloid A1. The PRRSV vaccine only affected haptoglobin. The pigs with positive viremia tended to show higher values than negative pigs, reaching significant differences in the three haptoglobin SRM-detected peptides but not with the data acquired by immunoenzymatic and spectrophotometric assays. These results open the door to the use of SRM to accurately monitor APP changes in experimental pigs.


Assuntos
Proteínas de Fase Aguda , Haptoglobinas , Síndrome Respiratória e Reprodutiva Suína , Vírus da Síndrome Respiratória e Reprodutiva Suína , Proteína Amiloide A Sérica , Vacinas Virais , Animais , Suínos , Vírus da Síndrome Respiratória e Reprodutiva Suína/imunologia , Síndrome Respiratória e Reprodutiva Suína/prevenção & controle , Síndrome Respiratória e Reprodutiva Suína/imunologia , Proteínas de Fase Aguda/análise , Proteínas de Fase Aguda/imunologia , Proteínas de Fase Aguda/metabolismo , Haptoglobinas/análise , Vacinas Virais/imunologia , Proteína Amiloide A Sérica/análise , Apolipoproteína A-I/imunologia , Apolipoproteína A-I/análise , Proteína C-Reativa/análise , Proteína C-Reativa/imunologia , Vacinação , Espectrometria de Massas/métodos , Viremia/prevenção & controle , Viremia/imunologia
13.
Int J Neuropsychopharmacol ; 27(7)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38970624

RESUMO

BACKGROUND: Alcohol use disorder (AUD) courses with inflammation and cognitive decline. Apolipoproteins have emerged as novel target compounds related to inflammatory processes and cognition. METHODS: A cross-sectional study was performed on abstinent AUD patients with at least 1 month of abstinence (n = 33; 72.7% men) and healthy controls (n = 34; 47.1% men). A battery of plasma apolipoproteins (APOAI, APOAII, APOB, APOCII, APOE, APOJ, and APOM), plasma inflammatory markers (LPS, LBP), and their influence on cognition and presence of the disorder were investigated. RESULTS: Higher levels of plasma APOAI, APOB, APOE, and APOJ, as well as the proinflammatory LPS, were observed in the AUD group, irrespective of sex, whereas APOM levels were lower vs controls. Hierarchical logistic regression analyses, adjusting for covariates (age, sex, education), associated APOM with the absence of cognitive impairment in AUD and identified APOAI and APOM as strong predictors of the presence or absence of the disorder, respectively. APOAI and APOM did not correlate with alcohol abuse variables or liver status markers, but they showed an opposite profile in their associations with LPS (positive for APOAI; negative for APOM) and cognition (negative for APOAI; positive for APOM) in the entire sample. CONCLUSIONS: The HDL constituents APOAI and APOM were differentially regulated in the plasma of AUD patients compared with controls, playing divergent roles in the disorder identification and associations with inflammation and cognitive decline.


Assuntos
Alcoolismo , Apolipoproteína A-I , Apolipoproteínas M , Disfunção Cognitiva , Inflamação , Humanos , Masculino , Feminino , Apolipoproteínas M/sangue , Projetos Piloto , Disfunção Cognitiva/sangue , Disfunção Cognitiva/etiologia , Pessoa de Meia-Idade , Estudos Transversais , Inflamação/sangue , Alcoolismo/sangue , Adulto , Apolipoproteína A-I/sangue , Biomarcadores/sangue , Apolipoproteínas/sangue
14.
Methods Mol Biol ; 2816: 205-222, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38977601

RESUMO

The role of lipid metabolic pathways in the pathophysiology of primary open-angle glaucoma (POAG) has been thoroughly elucidated, with pathways involved in lipid-related disorders such as hypercholesterolemia and hyperlipoprotein accumulation being of particular interest. The ABCA1/apoA-1 transduction pathway moderates reverse cholesterol transport (RCT), facilitating the transport of free cholesterol (FC) and phospholipids (PL) and preventing intracellular lipid aggregates in retinal ganglion cells (RGCs) due to excess FCs and PLs. A deficiency of ABCA1 transporters, and thus, dysregulation of the ABCA1/apoA-1 transduction pathway, may potentiate cellular lipid accumulation, which affects the structural and mechanical features of the cholesterol-rich RGC membranes. Atomic force microscopy (AFM) is a cutting-edge imaging technique suitable for imaging topographical surfaces of a biological specimen and determining its mechanical properties and structural features. The versatility and precision of this technique may prove beneficial in understanding the effects of ABCA1/apoA-1 pathway downregulation and decreased cholesterol efflux in RGCs and their membranes. In this protocol, ABCA1-/- RGC mouse models are prepared over the course of 3 days and are then compared with non-knockout ABCA1 RGC mouse models through AFM imaging of topographical surfaces to examine the difference in membrane dynamics of knockout vs. non-knockout models. Intracellular and extracellular levels of lipids are quantified through high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS).


Assuntos
Transportador 1 de Cassete de Ligação de ATP , Apolipoproteína A-I , Lipidômica , Microscopia de Força Atômica , Transdução de Sinais , Microscopia de Força Atômica/métodos , Animais , Camundongos , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Apolipoproteína A-I/metabolismo , Lipidômica/métodos , Colesterol/metabolismo , Camundongos Knockout , Metabolismo dos Lipídeos
15.
Front Endocrinol (Lausanne) ; 15: 1318416, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38919478

RESUMO

Background: Abnormal lipid levels have been associated with cancer incidence and progression. However, limited studies have investigated the relationship between apolipoprotein A-I (ApoA-I) and colorectal cancer (CRC). This study assessed the significance of ApoA-I levels in progression-free survival (PFS) and overall survival (OS) of patients with CRC. Methods: Survival curves were compared using Kaplan-Meier analysis, while the predictive values of various lipid indicators in CRC prognosis were evaluated based on receiver operating characteristic curves. The factors influencing PFS and OS in patients with CRC were analyzed using Cox proportional hazards regression models. Finally, the relationship between ApoA-I level and disease recurrence was investigated through logistic regression analysis. The optimal Apo-I level was determined through maximally selected rank statistics. Results: Using the optimal ApoA-I cutoff value (0.9 g/L), the 1,270 patients with CRC were categorized into low (< 0.9 g/L, 275 cases) and high (≥0.9 g/L, 995 cases) ApoA-I groups. Compared with other lipid indicators, ApoA-I demonstrated superior predictive accuracy. The high ApoA-I group exhibited significantly higher survival rates than the low ApoA-I group (PFS, 64.8% vs. 45.2%, P < 0.001; OS, 66.1% vs. 48.6%, P < 0.001). Each one-standard-deviation increase in ApoA-I level was related to a 12.0% decrease in PFS risk (hazard ratio [HR] 0.880; 95% confidence interval [CI], 0.801-0.968; P = 0.009) and an 11.2% decrease in OS risk (HR 0.888; 95%CI, 0.806-0.978; P = 0.015). Logistic regression analysis revealed that patients with low ApoA-I had a 32.5% increased risk of disease recurrence (odds ratio [OR] 0.675; 95%CI, 0.481-0.946; P = 0.0225) compared with those with high ApoA-I. PFS/OS nomograms based on ApoA-I demonstrated excellent prognostic prediction accuracy. Conclusions: Serum ApoA-I level may be a valuable and non-invasive tool for predicting PFS and OS in patients with CRC.


Assuntos
Apolipoproteína A-I , Neoplasias Colorretais , Humanos , Apolipoproteína A-I/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Prognóstico , Biomarcadores Tumorais/sangue , Taxa de Sobrevida , Adulto , Estimativa de Kaplan-Meier
16.
J Cell Mol Med ; 28(12): e18474, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38896027

RESUMO

Our previous study reckons that the impact of the rs1801133 variant of 5,10-methylenetetrahydrofolate reductase (MTHFR) on coronary artery disease (CAD) is possibly mediated by cardiometabolic disorder. This study is performed to verify this hypothesis. Four hundred and thirty CAD patients and 216 CAD-free individuals were enrolled in this case-control study. The rs1801133 variant was genotyped by PCR-RFLP. Severity of coronary lesions was evaluated by number of stenotic coronary vessels and extent of coronary stenosis. The rs1801133 T allele significantly increased homocysteine levels in patients with CAD and CAD-free individuals. Individuals with the T allele of rs1801133 had an increased risk of developing CAD. In contrast, individuals with the TT genotype of rs1801133 were at high risk of multiple vessel lesions. The carriers of CT genotype had higher levels of systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), and high-sensitivity C-reactive protein (hs-CRP), and lower levels of apolipoprotein A1 (APOA1) than those with CC genotype in male patients with CAD. The receiver operating characteristic (ROC) curve and precision-recall (PR) curve indicated that hyperhomocysteinemia was sensitive to predict the severity of CAD. Multivariate logistic regression revealed that homocysteine, rs1801133, age, smoking, weight, body mass index (BMI), lipoprotein(a) [Lp(a)], and hs-CRP were independent risk factors for CAD. The increased risk of CAD and severity of coronary lesions associated with rs1801133 in the Chinese Han population were attributed, at least partly, to high homocysteine levels. Hyperhomocysteinemia had a high predictive value for severe CAD or multiple vessel lesions.


Assuntos
Doença da Artéria Coronariana , Homocisteína , Metilenotetra-Hidrofolato Redutase (NADPH2) , Polimorfismo de Nucleotídeo Único , Humanos , Homocisteína/sangue , Masculino , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/patologia , Pessoa de Meia-Idade , Feminino , Estudos de Casos e Controles , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Índice de Gravidade de Doença , Idoso , Fatores de Risco , Predisposição Genética para Doença , Curva ROC , Genótipo , Proteína C-Reativa/metabolismo , Proteína C-Reativa/genética , Alelos , Apolipoproteína A-I/genética , Apolipoproteína A-I/sangue
17.
Front Endocrinol (Lausanne) ; 15: 1338698, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38863926

RESUMO

Background: Observational studies suggest an association between telomere length (TL) and blood lipid (BL) levels. Nevertheless, the causal connections between these two traits remain unclear. We aimed to elucidate whether genetically predicted TL is associated with BL levels via Mendelian randomization (MR) and vice versa. Methods: We obtained genetic instruments associated with TL, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A-1 (ApoA-1) and apolipoprotein B (ApoB) from large-scale genome-wide association studies (GWASs). The causal relationships between TL and BL were investigated via bidirectional MR, multivariable MR and mediation analysis methods. The inverse variance weighted (IVW) method was employed as the principal methodology, complemented by several other estimators to enhance the robustness of the analysis. Results: In the forward MR analyses, we identified significant positive correlation between genetically predicted TL and the levels of TG (ß=0.04, 95% confidence interval [CI]: 0.01 to 0.06, p = 0.003). In the reverse MR analysis, TG (ß=0.02, 95% CI: 0.01 to 0.03, p = 0.004), LDL-C (ß=0.03, 95% CI: 0.01 to 0.04, p = 0.001) and ApoB (ß=0.03, 95% CI: 0.01 to 0.04, p = 9.71×10-5) were significantly positively associated with TL, although this relationship was not observed in the multivariate MR analysis. The mediation analysis via two-step MR showed no significant mediation effects acting through obesity-related phenotypes in analysis of TL with TG, while the effect of LDL-C on TL was partially mediated by body mass index (BMI) in the reverse direction, with mediated proportion of 12.83% (95% CI: 0.62% to 25.04%). Conclusions: Our study indicated that longer TL were associated with higher TG levels, while conversely, higher TG, LDL-C, and ApoB levels predicted longer TL, with BMI partially mediating these effects. Our findings present valuable insights into the development of preventive strategies and interventions that specifically target TL-related aging and age-related diseases.


Assuntos
Estudo de Associação Genômica Ampla , Lipídeos , Análise da Randomização Mendeliana , Humanos , Lipídeos/sangue , LDL-Colesterol/sangue , Triglicerídeos/sangue , Telômero/genética , HDL-Colesterol/sangue , Polimorfismo de Nucleotídeo Único , Homeostase do Telômero , Apolipoproteína A-I/sangue , Apolipoproteína A-I/genética
18.
J Immunol ; 213(4): 456-468, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38912868

RESUMO

Neutrophils play important roles in inflammatory airway diseases. In this study, we assessed whether apolipoprotein A-I modifies neutrophil heterogeneity as part of the mechanism by which it attenuates acute airway inflammation. Neutrophilic airway inflammation was induced by daily intranasal administration of LPS plus house dust mite (LPS+HDM) to Apoa1-/- and Apoa1+/+ mice for 3 d. Single-cell RNA sequencing was performed on cells recovered from bronchoalveolar lavage fluid on day 4. Unsupervised profiling identified 10 clusters of neutrophils in bronchoalveolar lavage fluid from Apoa1-/- and Apoa1+/+ mice. LPS+HDM-challenged Apoa1-/- mice had an increased proportion of the Neu4 neutrophil cluster that expressed S100a8, S100a9, and Mmp8 and had high maturation, aggregation, and TLR4 binding scores. There was also an increase in the Neu6 cluster of immature neutrophils, whereas neutrophil clusters expressing IFN-stimulated genes were decreased. An unsupervised trajectory analysis showed that Neu4 represented a distinct lineage in Apoa1-/- mice. LPS+HDM-challenged Apoa1-/- mice also had an increased proportion of recruited airspace macrophages, which was associated with a reciprocal reduction in resident airspace macrophages. Increased expression of a common set of proinflammatory genes, S100a8, S100a9, and Lcn2, was present in all neutrophils and airspace macrophages from LPS+HDM-challenged Apoa1-/- mice. These findings show that Apoa1-/- mice have increases in specific neutrophil and macrophage clusters in the lung during acute inflammation mediated by LPS+HDM, as well as enhanced expression of a common set of proinflammatory genes. This suggests that modifications in neutrophil and macrophage heterogeneity contribute to the mechanism by which apolipoprotein A-I attenuates acute airway inflammation.


Assuntos
Apolipoproteína A-I , Camundongos Knockout , Neutrófilos , Pneumonia , Animais , Camundongos , Neutrófilos/imunologia , Pneumonia/imunologia , Pneumonia/genética , Apolipoproteína A-I/genética , Camundongos Endogâmicos C57BL , Lipopolissacarídeos/imunologia , Líquido da Lavagem Broncoalveolar/imunologia , Líquido da Lavagem Broncoalveolar/citologia , Pulmão/imunologia , Pulmão/patologia , Calgranulina A , Calgranulina B
19.
Clin Rheumatol ; 43(8): 2513-2520, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38877375

RESUMO

This study is asked to investigate the effects of belimumab on the lipid profile in systemic lupus erythematosus (SLE) patients. Forty-one SLE patients who received at least 6 months of belimumab treatment were retrospectively analyzed. The control group consisted of 56 age- and sex-matched lupus patients not treated with belimumab. The changes in lipid profile after a 6-month treatment were compared between the two groups. Generalized estimating equation (GEE) analyses were performed to examine lipid levels longitudinally during the period and the effect of clinical response variables and medication on the lipid profile in the belimumab group. In the belimumab group, high-density lipoprotein (HDL) cholesterol levels increased significantly after the 6-month treatment (P = 0.02). After 1 month, HDL, apolipoprotein A-I (apoA-I) significantly increased by 13.8 and 11.4%, compared with baseline, respectively. After 3 months, HDL and apoA-I increased by 9.0 and 7.1%, respectively. After 6 months, HDL increased by 7.6% compared with baseline. Total cholesterol, triglycerides, low-density lipoprotein cholesterol, and apolipoprotein B did not change significantly over the course of treatment. GEE analyses indicated a significant association between HDL and disease activity indexes, such as IgG, anti-dsDNA, and complement C3. Subgroup analysis revealed significant changes in HDL only in patients who had achieved a ≥ 4-point reduction in SLEDAI-2 K after 6 months of belimumab treatment. Belimumab treatment may result in a long-term increase in HDL level in SLE patients by improving control of lupus activity. This might have beneficial effects on controlling cardiovascular risk in lupus patients. Key Points • Treatment with belimumab resulted in a significant and sustained increase in the HDL levels in SLE patients. • Significant changes in HDL were observed in lupus patients treated with belimumab who had a better clinical response.


Assuntos
Anticorpos Monoclonais Humanizados , HDL-Colesterol , Imunossupressores , Lipídeos , Lúpus Eritematoso Sistêmico , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/sangue , Anticorpos Monoclonais Humanizados/uso terapêutico , Feminino , Adulto , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , HDL-Colesterol/sangue , Imunossupressores/uso terapêutico , Lipídeos/sangue , Apolipoproteína A-I/sangue , Triglicerídeos/sangue , Resultado do Tratamento , LDL-Colesterol/sangue
20.
Circ Res ; 135(2): 335-349, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38828596

RESUMO

BACKGROUND: Individuals with type 1 diabetes (T1D) generally have normal or even higher HDL (high-density lipoprotein)-cholesterol levels than people without diabetes yet are at increased risk for atherosclerotic cardiovascular disease (CVD). Human HDL is a complex mixture of particles that can vary in cholesterol content by >2-fold. To investigate if specific HDL subspecies contribute to the increased atherosclerosis associated with T1D, we created mouse models of T1D that exhibit human-like HDL subspecies. We also measured HDL subspecies and their association with incident CVD in a cohort of people with T1D. METHODS: We generated LDL receptor-deficient (Ldlr-/-) mouse models of T1D expressing human APOA1 (apolipoprotein A1). Ldlr-/-APOA1Tg mice exhibited the main human HDL subspecies. We also generated Ldlr-/-APOA1Tg T1D mice expressing CETP (cholesteryl ester transfer protein), which had lower concentrations of large HDL subspecies versus mice not expressing CETP. HDL particle concentrations and sizes and proteins involved in lipoprotein metabolism were measured by calibrated differential ion mobility analysis and targeted mass spectrometry in the mouse models of T1D and in a cohort of individuals with T1D. Endothelial transcytosis was analyzed by total internal reflection fluorescence microscopy. RESULTS: Diabetic Ldlr-/-APOA1Tg mice were severely hyperglycemic and hyperlipidemic and had markedly elevated plasma APOB levels versus nondiabetic littermates but were protected from the proatherogenic effects of diabetes. Diabetic Ldlr-/-APOA1Tg mice expressing CETP lost the atheroprotective effect and had increased lesion necrotic core areas and APOB accumulation, despite having lower plasma APOB levels. The detrimental effects of low concentrations of larger HDL particles in diabetic mice expressing CETP were not explained by reduced cholesterol efflux. Instead, large HDL was more effective than small HDL in preventing endothelial transcytosis of LDL mediated by scavenger receptor class B type 1. Finally, in humans with T1D, increased concentrations of larger HDL particles relative to APOB100 negatively predicted incident CVD independently of HDL-cholesterol levels. CONCLUSIONS: Our results suggest that the balance between APOB lipoproteins and the larger HDL subspecies contributes to atherosclerosis progression and incident CVD in the setting of T1D and that larger HDLs exert atheroprotective effects on endothelial cells rather than by promoting macrophage cholesterol efflux.


Assuntos
Apolipoproteína A-I , Aterosclerose , Diabetes Mellitus Tipo 1 , Receptores de LDL , Adulto , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Apolipoproteína A-I/sangue , Apolipoproteína A-I/metabolismo , Apolipoproteína B-100/metabolismo , Apolipoproteína B-100/genética , Apolipoproteína B-100/sangue , Aterosclerose/metabolismo , Aterosclerose/genética , Aterosclerose/sangue , Aterosclerose/patologia , Proteínas de Transferência de Ésteres de Colesterol/genética , Proteínas de Transferência de Ésteres de Colesterol/metabolismo , Proteínas de Transferência de Ésteres de Colesterol/sangue , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/sangue , Modelos Animais de Doenças , Lipoproteínas HDL/sangue , Lipoproteínas HDL/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Receptores de LDL/genética , Receptores de LDL/deficiência , Receptores de LDL/metabolismo
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