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‣ Lipoproteína(a) na síndrome antifosfolípide primária; Lipoprotein(a) in primary antiphospholipid syndrome

CARVALHO, Jozélio Freire de; CALEIRO, Maria Teresa Correia
Fonte: Elsevier Editora Ltda Publicador: Elsevier Editora Ltda
Tipo: Artigo de Revista Científica
Português
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OBJETIVO: Avaliar níveis de lipoproteína(a) em pacientes com síndrome antifosfolípide primária (SAFP) e suas possíveis associações clínicas e laboratoriais. MÉTODOS: Estudo transversal de 46 pacientes (93,5% do sexo feminino) com SAFP (critérios de Sapporo). Foram avaliados os dados demográficos e clínicos, medicações, anticorpos antifosfolípides, além da medida dos níveis séricos em jejum da lipoproteína(a). RESULTADOS: Os níveis de lipoproteína(a) ( > 30 mg/dL) foram vistos em 43,5% dos pacientes com SAFP, com média de 42 ± 43,5 mg/dL. Comparando-se o grupo com níveis maiores que 30 mg/dL com o grupo de pacientes com níveis menores ou iguais a este valor, não foram observadas diferenças significativas em relação a dados demográficos (idade, sexo, cor branca, peso, altura e índice de massa corporal), manifestações da doença (eventos arteriais, venosos, obstétricos, plaquetopenia), eventos cardiovasculares (infarto agudo do miocárdio, angina, acidente vascular cerebral), comorbidades, estilo de vida (atividade física, tabagismo atual e pregresso), uso de medicações (corticoide atual e pregresso, estatina, cloroquina), bem como à frequência de positividade de anticorpos antifosfolípides. CONCLUSÃO: Pacientes com SAFP apresentam uma frequência elevada de níveis aumentados de lipoproteína(a). Entretanto...

‣ Lipoprotein (a): Structure, Pathophysiology and Clinical Implications

Maranhão,Raul Cavalcante; Carvalho,Priscila Oliveira; Strunz,Celia Cassaro; Pileggi,Fulvio
Fonte: Sociedade Brasileira de Cardiologia - SBC Publicador: Sociedade Brasileira de Cardiologia - SBC
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/07/2014 Português
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The chemical structure of lipoprotein (a) is similar to that of LDL, from which it differs due to the presence of apolipoprotein (a) bound to apo B100 via one disulfide bridge. Lipoprotein (a) is synthesized in the liver and its plasma concentration, which can be determined by use of monoclonal antibody-based methods, ranges from < 1 mg to > 1,000 mg/dL. Lipoprotein (a) levels over 20-30 mg/dL are associated with a two-fold risk of developing coronary artery disease. Usually, black subjects have higher lipoprotein (a) levels that, differently from Caucasians and Orientals, are not related to coronary artery disease. However, the risk of black subjects must be considered. Sex and age have little influence on lipoprotein (a) levels. Lipoprotein (a) homology with plasminogen might lead to interference with the fibrinolytic cascade, accounting for an atherogenic mechanism of that lipoprotein. Nevertheless, direct deposition of lipoprotein (a) on arterial wall is also a possible mechanism, lipoprotein (a) being more prone to oxidation than LDL. Most prospective studies have confirmed lipoprotein (a) as a predisposing factor to atherosclerosis. Statin treatment does not lower lipoprotein (a) levels, differently from niacin and ezetimibe...

‣ Etofibrate but not controlled-release niacin decreases LDL cholesterol and lipoprotein (a) in type IIb dyslipidemic subjects

Sposito,A.C.; Mansur,A.P.; Maranhão,R.C.; Rodrigues-Sobrinho,C.R.M.; Coelho,O.R.; Ramires,J.A.F.
Fonte: Associação Brasileira de Divulgação Científica Publicador: Associação Brasileira de Divulgação Científica
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/02/2001 Português
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Etofibrate is a hybrid drug which combines niacin with clofibrate. After contact with plasma hydrolases, both constituents are gradually released in a controlled-release manner. In this study, we compared the effects of etofibrate and controlled-release niacin on lipid profile and plasma lipoprotein (a) (Lp(a)) levels of patients with triglyceride levels of 200 to 400 mg/dl, total cholesterol above 240 mg/dl and Lp(a) above 40 mg/dl. These patients were randomly assigned to a double-blind 16-week treatment period with etofibrate (500 mg twice daily, N = 14) or niacin (500 mg twice daily, N = 11). In both treatment groups total cholesterol, VLDL cholesterol and triglycerides were equally reduced and high-density lipoprotein cholesterol was increased. Etofibrate, but not niacin, reduced Lp(a) by 26% and low-density lipoprotein (LDL) cholesterol by 23%. The hybrid compound etofibrate produced a more effective reduction in plasma LDL cholesterol and Lp(a) levels than controlled-release niacin in type IIb dyslipidemic subjects.

‣ Lipoprotein (a) and cardiovascular risk factors in children and adolescents

Palmeira,Ástrid Camêlo; Leal,Adriana Amorim de F.; Ramos,Nathaly de Medeiros N.; F. Neto,José de Alencar; Simões,Mônica Oliveira da S.; Medeiros,Carla Campos M.
Fonte: Sociedade de Pediatria de São Paulo Publicador: Sociedade de Pediatria de São Paulo
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/12/2013 Português
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OBJECTIVE: To review the relationship between lipoprotein (a) [Lp(a)] and other risk factors for cardiovascular disease (CVD) in children and adolescents. DATA SOURCES: This systematic review included studies from 2001 to 2011, a ten-year time period. Epidemiological studies with children and/or adolescents published in English, Portuguese or Spanish and fully available online were included. The searches were performed in Science Direct, PubMed/Medline, BVS (Biblioteca Virtual em Saúde) and Cochrane Library databases, using the following combination of key-words: "lipoprotein a" and "cardiovascular diseases" and "obesity". DATA SYNTHESIS: Overall, 672 studies were obtained but only seven were included. Some studies assessed the family history for CVD. In all of them, Lp(a) levels were increased in patients with family history for CVD. There was also a positive correlation between Lp(a) and LDL-cholesterol, total cholesterol, and apolipoprotein B levels, suggesting an association between Lp(a) levels and the lipid profile. CONCLUSIONS: The evidence that CVD may originate in childhood and adolescence leads to the need for investigating the risk factors during this period in order to propose earlier and possibly more effective interventions to reduce morbidity and mortality rates.

‣ The involvement of multiple thrombogenic and atherogenic markers in premature coronary artery disease

Mansur,Antonio P.; Takada,Julio Y.; Strunz,Celia M. C.; Avakian,Solange D.; Cesar,Luiz Antonio M.; Ramires,Jose A.F.
Fonte: Faculdade de Medicina / USP Publicador: Faculdade de Medicina / USP
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/12/2013 Português
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OBJECTIVE: To examine the association of atherogenic and thrombogenic markers and lymphotoxin-alfa gene mutations with the risk of premature coronary disease. METHODS: This cross-sectional, case-control, age-adjusted study was conducted in 336 patients with premature coronary disease (<50 years old) and 189 healthy controls. The control subjects had normal clinical, resting, and exercise stress electrocardiographic assessments. The coronary disease group patients had either angiographically documented disease (>50% luminal reduction) or a previous myocardial infarction. The laboratory data evaluated included thrombogenic factors (fibrinogen, protein C, protein S, and antithrombin III), atherogenic factors (glucose and lipid profiles, lipoprotein(a), and apolipoproteins AI and B), and lymphotoxin-alfa mutations. Genetic variability of lymphotoxin-alfa was determined by polymerase chain reaction analysis. RESULTS: Coronary disease patients exhibited lower concentrations of HDL-cholesterol and higher levels of glucose, lipoprotein(a), and protein S. The frequencies of AA, AG, and GG lymphotoxin-alfa mutation genotypes were 55.0%, 37.6%, and 7.4% for controls and 42.7%, 46.0%, and 11.3% for coronary disease patients (p = 0.02)...

‣ Serum lipoprotein(a) concentrations are related to coronary disease progression without new myocardial infarction.

Tamura, A.; Watanabe, T.; Mikuriya, Y.; Nasu, M.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /10/1995 Português
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OBJECTIVE--To examine the association between serum lipoprotein(a) and angiographically assessed coronary artery disease progression without new myocardial infarction. PATIENTS AND DESIGN--85 patients with coronary artery disease who underwent serial angiography with an interval of at least two years were studied. Progression of coronary artery disease was defined as an increase in diameter stenosis of 15% or more. Vessels on which angioplasty had been performed were excluded from the analysis. The patients were classified into two groups: a progression group without new myocardial infarction (n = 48) and non-progression group (n = 37). Risk factors including lipoprotein(a) were evaluated to see how they were related to progression without myocardial infarction. RESULTS--There were no differences between the two groups in the following factors: age, gender, the time interval between the angiographic studies, the distribution of the analysed coronary arteries, and history of well established coronary risk factors. Univariate analysis showed that serum lipoprotein(a) (P = 0.0002), cigarette smoking between the studies (P = 0.002), serum high density lipoprotein (P = 0.003), and serum low density lipoprotein (P = 0.01) were related to progression without myocardial infarction. Multivariate analysis selected two independent factors for progression without myocardial infarction: serum lipoprotein(a) (P = 0.003) and serum high density lipoprotein (P = 0.03). CONCLUSIONS--Serum lipoprotein(a) concentrations are closely related to the progression of coronary artery disease without new myocardial infarction. Lipoprotein(a) lowering treatment may be needed to prevent disease progression in patients with coronary artery disease and high serum lipoprotein(a).

‣ Detection of new epitopes formed upon oxidation of low-density lipoprotein, lipoprotein (a) and very-low-density lipoprotein. Use of an antiserum against 4-hydroxynonenal-modified low-density lipoprotein.

Jürgens, G; Ashy, A; Esterbauer, H
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 15/01/1990 Português
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4-Hydroxynonenal (HNE) is a major aldehydic propagation product formed during peroxidation of unsaturated fatty acids. The aldehyde was used to modify freshly prepared human low-density lipoprotein (LDL). A polyclonal antiserum was raised in the rabbit and absorbed with freshly prepared LDL. The antiserum did not react with human LDL, but reacted with CuCl2-oxidized LDL and in a dose-dependent manner with LDL, modified with 1, 2 and 3 mM-HNE, in the double-diffusion analysis. LDL treated with 4 mM of hexanal or hepta-2,4-dienal or 4-hydroxyhexenal or malonaldehyde (4 or 20 mM) did not react with the antiserum. However, LDL modified with 4 mM-4-hydroxyoctenal showed a very weak reaction. Lipoprotein (a) and very-low-density lipoprotein were revealed for the first time to undergo oxidative modification initiated by CuCl2. This was evidenced by the generation of lipid hydroperoxides and thiobarbituric acid-reactive substances, as well as by a marked increase in the electrophoretic mobility. After oxidation these two lipoproteins also reacted positively with the antiserum against HNE-modified LDL.

‣ Proposed mechanisms for binding of apo[a] kringle type 9 to apo B-100 in human lipoprotein[a].

Guevara, J; Spurlino, J; Jan, A Y; Yang, C Y; Tulinsky, A; Prasad, B V; Gaubatz, J W; Morrisett, J D
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /03/1993 Português
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The protein component of human lipoprotein[a] consists primarily of two apolipoproteins, apo[a] and apo B-100, linked through a cystine disulfide(s). In the amino acid sequence of apo bd, Cys4057 located within a plasminogen kringle 4-like repeat sequence (3991-4068) is believed to form a disulfide bond with a specific cysteine residue in apo B-100. Our fluorescence-labeling experiments and molecular modeling studies have provided evidence for possible interactions between this apo[a] kringle type and apo B-100. The fluorescent probe, fluorescein-5-maleimide, was used in parallel experiments to label free sulfhydryl moieties in lipoprotein[a] and low-density lipoprotein (LDL). In apo B-100 of LDL, Cys3734 was labeled with the probe, but this site was not labeled in autologous lipoprotein[a]. The result strongly implicates Cys3734 of apo B-100 as the residue forming the disulfide linkage with Cys4057 of apo[a]. To explore possible noncovalent interactions between apo B-100 and apo[a], the crystallographic coordinates for plasminogen kringle 4 were used to generate molecular models of the apo[a] kringle-repeat sequence (3991-4068, LPaK9), the only plasminogen kringle 4 type repeat in apo[a] having an extra cysteine residue not involved in an intramolecular disulfide bond. The Cys4057 residue (henceforth designated as Cys67 in the LPaK9 sequence) is believed to form an intermolecular disulfide bond with a cysteine of apo B-100. In computer graphics molecular models of LPaK9...

‣ Lipoprotein (a) and coronary heart disease: a prospective case-control study in a general population sample of middle aged men.

Rosengren, A; Wilhelmsen, L; Eriksson, E; Risberg, B; Wedel, H
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 01/12/1990 Português
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OBJECTIVE--To examine the association between the serum lipoprotein (a) concentration and subsequent coronary heart disease. DESIGN--Prospective case-control study based on a six year follow up of a general population sample of men aged 50 at baseline in 1983-4. Serum samples were frozen at the time of the baseline examination and kept at -70 degrees C for six years, after which the lipoprotein (a) concentrations in the samples were measured in cases and controls. SETTING--City of Gothenburg, Sweden. SUBJECTS--26 Men, from a general population sample of 776 men, who had sustained a myocardial infarction or died of coronary heart disease during the six years and 109 randomly selected controls from the same sample who had remained free of myocardial infarction. In neither cases nor controls was there a history of myocardial infarction at baseline. MAIN OUTCOME MEASURES--Proportion of myocardial infarction or deaths from coronary heart disease, or both, in relation to the serum lipoprotein (a) concentration. RESULTS--Men who suffered coronary heart disease had significantly higher serum lipoprotein (a) concentrations than controls (mean difference 105 mg/l; 95% confidence interval 18 to 192 mg/l). Men with the highest fifth of serum lipoprotein (a) concentrations (cut off point 365 mg/l) suffered a coronary heart disease rate which was more than twice that of men with the lowest four fifths of concentrations. Logistic regression analysis showed the serum lipoprotein (a) concentration to be significantly associated with coronary heart disease independently of other risk factors. CONCLUSION--The serum lipoprotein (a) concentration in middle aged men is an independent risk factor for subsequent myocardial infarction or death from coronary heart disease.

‣ Lipoprotein (a) concentrations as risk indicators for atherosclerosis.

Kostner, G M; Czinner, A; Pfeiffer, K H; Bihari-Varga, M
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /09/1991 Português
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The plasma concentration of different lipoproteins were measured in 102 control children, in 42 children with a parent suffering from coronary heart disease (CHD), and in 50 children with a parent with cerebrovascular disease (CVD). Significant differences between controls and children in the other two groups were found for apolipoprotein A I, apolipoprotein B, and high density lipoprotein-cholesterol. Children of parents with CHD differed from controls in total cholesterol and apolipoprotein A II concentrations. A highly significant difference furthermore was found in lipoprotein (a) concentrations from children of parents with CHD in comparison with controls, but not between children of parents with CVD and controls. The difference in lipoprotein (a) concentrations (children of parents with CHD compared with controls) were only noticed in children above the age of 10 years. This could be explained by the observed rise of lipoprotein (a) between age 2 and 13 years, which was much more pronounced in the group with parents who had CHD. Plasma glycosaminoglycan concentrations were also measured in the three groups. They were significantly higher in children of parents with CHD and CVD compared with controls; they also varied with age.

‣ Levels of Lipoprotein(a), Apolipoprotein B, and Lipoprotein Cholesterol Distribution in IDDM: Results From Follow-up in the Diabetes Control and Complications Trial

Purnell, Jonathan Q.; Marcovina, Santica M.; Hokanson, John E.; Kennedy, Hal; Cleary, Patricia A.; Steffes, Michael W.; Brunzell, John D.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /10/1995 Português
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Levels of lipoprotein (a) [Lp(a)], apolipoprotein (apo) B, and lipoprotein cholesterol distribution using density-gradient ultracentrifugation were measured as part of a cross-sectional study at the final follow-up examination (mean 6.2 years) in the Diabetes Control and Complications Trial. Compared with the subjects in the conventionally treated group (n = 680), those subjects receiving intensive diabetes therapy (n = 667) had a lower level of Lp(a) (Caucasian subjects only, median 10.7 vs. 12.5 mg/dl, respectively; P = 0.03), lower apo B (mean 83 vs. 86 mg/dl, respectively; P = 0.01), and a more favorable distribution of cholesterol in the lipoprotein fractions as measured by density-gradient ultracentrifugation with less cholesterol in the very-low-density lipoprotein and the dense low-density lipoprotein fractions and greater cholesterol content of the more buoyant low-density lipoprotein. Compared with a nondiabetic Caucasian control group (n = 2,158), Lp(a) levels were not different in the intensive treatment group (median 9.6 vs. 10.7 mg/dl, respectively; NS) and higher in the conventional treatment group (9.6 vs. 12.5 mg/dl, respectively; P less than 0.01). No effect of renal dysfunction as measured by increasing albuminuria or reduced creatinine clearance on Lp(a) levels could be demonstrated in the diabetic subjects. Prospective follow-up of these subjects will determine whether these favorable lipoprotein differences in the intensive treatment group persist and whether they influence the onset of atherosclerosis in insulin-dependent diabetes.

‣ Elevated lipoprotein (a), small apolipoprotein (a), and the risk of arterial ischemic stroke in North American children

Goldenberg, Neil A.; Bernard, Timothy J.; Hillhouse, Jasper; Armstrong-Wells, Jennifer; Galinkin, Jeffrey; Knapp-Clevenger, Rhonda; Jacobson, Linda; Marcovina, Santica M.; Manco-Johnson, Marilyn J.
Fonte: Ferrata Storti Foundation Publicador: Ferrata Storti Foundation
Tipo: Artigo de Revista Científica
Publicado em /05/2013 Português
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Lipoprotein (a) is a risk factor for adult cardiovascular events, in which the apolipoprotein (a) component is thought to promote atherogenesis and impair fibrinolysis. We investigated whether elevated plasma lipoprotein (a) concentration and small predominant apolipoprotein (a) isoform size (number of kringle-4 domains) are risk factors for childhood arterial ischemic stroke and correlate with plasma fibrinolytic function. Patients who had had an arterial ischemic stroke in childhood (29 days - <21 years at onset; n=43) and healthy controls (n=127) were recruited for plasma sampling and laboratory determinations. Cases were followed for recurrence in a prospective cohort study. The median lipoprotein (a) concentration did not differ between groups [cases: median 18.0 nmol/L (7.5 mg/dL) and observed range 0.9–259 nmol/L (0.38–108.0 mg/dL), controls: 20.4 nmol/L (8.5 mg/dL) and 0.2–282 nmol/L (0.08–117.5 mg/dL); P=0.62]. While odds of incident stroke were not significantly increased, risks of recurrent arterial ischemic stroke were each more than ten-times increased for lipoprotein(a) >90th percentile of race-specific reference values and apolipoprotein (a) <10th percentiles [odds ratio=14.0 (95% confidence interval: 1.0–184)...

‣ Review of Lipid and Lipoprotein(a) Abnormalities in Childhood Arterial Ischemic Stroke

Sultan, Sally M; Schupf, Nicole; Dowling, Michael M.; DeVeber, Gabrielle A.; Kirton, Adam; Elkind, Mitchell S.V.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
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National organizations recommend cholesterol screening in children to prevent vascular disease in adulthood. There are currently no recommendations for cholesterol and lipoprotein (a) testing in children who experience an arterial ischemic stroke. While dyslipidemia and elevated lipoprotein (a) are associated with ischemic stroke in adults, the role of atherosclerotic risk factors in childhood arterial ischemic stroke is not known. A review of the literature was performed from 1966- 4/2012 to evaluate the association between childhood arterial ischemic stroke and dyslipidemia or elevated lipoprotein (a). Of 239 citations, there were 16 original observational studies in children (with or without neonates,) with imaging-confirmed arterial ischemic stroke and data on cholesterol or lipoprotein (a) values. Three pairs of studies reported overlapping subjects, and 2 were eliminated. Among 14 studies, there was data on cholesterol in 7 and lipoprotein (a) in 10. After stroke, testing was performed at > 3 months in 9 studies, at ≤3 months in 4 studies and not specified in one study. There were 5 case-control studies: 4 compared elevated lipoprotein (a) and one compared abnormal cholesterol in children with arterial ischemic stroke to controls. A consistent positive association between elevated lipoprotein (a) and stroke was found [Mantel-Haenszel OR 4.24 (2.94–6.11)]. There was no association in one study on total cholesterol...

‣ Longitudinal study of lipoprotein (a) in peripubertal children with insulin dependent diabetes

Couper, J.; Cocciolone, R.; Bates, D.; Nairn, J.; Ryall, R.
Fonte: JOHN WILEY & SONS LTD Publicador: JOHN WILEY & SONS LTD
Tipo: Artigo de Revista Científica
Publicado em //1995 Português
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We aimed to examine the longitudinal relationship between lipoprotein(a) and haemoglobin A1c, albumin excretion rate, and puberty in peripubertal children with insulin-dependent diabetes. A total of 114 patients aged 11.5 +/- 3.6 years (mean (SD)) were followed prospectively for 15.2 +/- 2.8 months. Lipoprotein(a), apolipoproteinB-100, haemoglobin A1c, mean overnight albumin excretion rate and Tanner stage were determined at the beginning and end of the study period. Lipoprotein(a) and apolipoproteinB-100 were measured using nephelometry. This method was correlated with radioimmunoassay and there was no significant change in mean bias during the study. Lipoprotein(a) fell significantly over time (214, (152, 276); 160 (84, 236) mg l-1 geometric mean (0.95 confidence intervals), p < 0.001); apolipoproteinB-100 did not change. Lipoprotein(a) and apolipoproteinB-100 did not differ in 233 cross-sectional controls of similar age. The change in lipoprotein(a) did not correlate with a small fall in haemoglobin A1c or with overnight albumin excretion rate, Tanner stage or insulin dose. Separate analysis of male and female patients and prepubertal and pubertal patients continued to show a significant fall in lipoprotein(a) independent of change in haemoglobin A1c or albumin excretion rate. Likewise...

‣ COVALENT LIPOPROTEIN(A) ASSEMBLY: Characterization of Oxidase Activity Responsible for Catalyzing Covalent Lipoprotein(a) Assembly

Sledziecka, Anna
Fonte: Quens University Publicador: Quens University
Tipo: Tese de Doutorado Formato: 9255184 bytes; application/pdf
Português
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66.69685%
Lipoprotein(a) (Lp(a)) has been identified as an emerging risk factor for the development of vascular diseases. The Lp(a) particle is assembled in a 2-step process upon secretion of the LDL and apo(a) components from hepatocytes. Work done by the Koschinsky group has identified an oxidase-like activity present in the conditioned medium (CM) harvested from human hepatoma (HepG2), as well as HEK 293 (human endothelian kidney) cells that catalyzes the rate of covalent Lp(a) formation. We have taken a candidate enzyme approach to identifying this oxidase activity. Specifically, we have proposed that the QSOX (Quiescin/sulfhydryl oxidase) is responsible for catalysis of covalent Lp(a) assembly. An oxidase activity assay developed by Dr. Thorpe (University of Delaware) was used to detect QSOX1 in CM harvested from cultured cell lines that catalyze covalent Lp(a) assembly. In addition, the QSOX1 transcript was identified in each cell line and quantified with the use of Real-Time RT-PCR. Quantitative assays of covalent Lp(a) assembly were performed to study some characteristics of the unkwown oxidase activity. First, conditioned medium was dialyzed through a 5 kDa cutoff, as this has previously been shown to reduce the aforementioned oxidase activity. Purified QSOX was then added back to the reaction and the rate of catalysis was observed. The addition of QSOX appeared to enhance the rate of covalent Lp(a) assembly in a dose-dependent manner. Additional covalent Lp(a) assembly assays were performed where various chemicals were added to determine whether Lp(a) assembly was affected. The addition of EDTA did not affect covalent assembly...

‣ EFFECTS OF Apolipoprotein(a) ON VASCULAR ENDOTHELIAL CELL FUNCTION: INSIGHTS INTO POSSIBLE PHYSIOLOGICAL AND/OR PATHOLOGICAL ROLES FOR Lipoprotein(a)

LIU, LEI
Fonte: Quens University Publicador: Quens University
Tipo: Tese de Doutorado Formato: 4323489 bytes; application/pdf
Português
Relevância na Pesquisa
66.58609%
Numerous studies have identified that elevated plasma concentrations of lipoprotein(a) [Lp(a)] are an emerging risk factor for a variety of atherothrombotic disorders. Apolipoprotein(a) [apo(a)], the unique glycoprotein component of Lp(a), consists of tandem repeats of a plasminogen kringle (K) IV-like domain, followed by sequences homologous to the plasminogen KV and protease domains. Apo(a)/Lp(a) has been consistently shown to regulate endothelial function and inhibit plasminogen activation. In the present study, we have demonstrated that apo(a), signaling via integrin alphaVbeta3, is the functional unit in Lp(a) to stimulate in vitro endothelial cell (EC) proliferation and migration, and activate focal adhesion kinase (FAK) and mitogen-activated protein kinases (MAPK) in cultured ECs. Both apo(a) and Lp(a) have also been shown to reduce the levels of active and total transforming growth factor (TGF)-beta in cultured EC medium in an integrin alphaVbeta3–dependent manner. Despite the stimulatory effects of apo(a) on EC proliferation and migration, we have further confirmed an inhibitory effect of apo(a) on EC in vitro angiogenesis using a fibrin gel tube formation assay. We have provided evidence proving apo(a) inhibits angiogenesis through inhibition of plasminogen activation...

‣ Analysis of Lipoprotein(a) Catabolism

Theuerle, James Douglas
Fonte: Quens University Publicador: Quens University
Tipo: Tese de Doutorado Formato: 2193810 bytes; application/pdf
Português
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Elevated plasma concentrations of lipoprotein(a) [Lp(a)] have been identified as an independent risk factor for vascular diseases including coronary heart disease and stroke. In the current study, we have examined the binding and degradation of recombinant forms of apolipoprotein(a) [r-apo(a)], the unique kringle-containing moiety of Lp(a), using a cultured cell model. We found that the incubation of human hepatoma (HepG2) cells with an iodinated 17 kringle-containing (17K) recombinant form of apo(a) resulted in a two-component binding system characterized by a high affinity (Kd = 12 nM), low capacity binding site, and a low affinity (Kd = 249 nM), high capacity binding site. We subsequently determined that the high affinity binding site on HepG2 cells corresponds to the LDL receptor. In the HepG2 cell model, association of apo(a) with the LDL receptor was shown to be dependent on the formation of Lp(a) particles from endogenous LDL. Using an apo(a) mutant incapable of binding to the high affinity site through its inability to form Lp(a) particles (17KΔLBS7,8), we further demonstrated that the LDL receptor does not participate in Lp(a) catabolism. The low affinity binding component observed on HepG2 cells, familial hypercholesterolemia (FH) fibroblasts and human embryonic kidney (HEK) 293 cells may correspond to a member(s) of the plasminogen receptor family...

‣ Plasma lipoprotein(a) levels: a comparison between diabetic and non-diabetic patients with acute ischemic stroke

Holanda,Maurus Marques de Almeida; Filizola,Rosália Gouveia; Costa,Maria José de Carvalho; Andrade,Rodrigo Vasconcelos C.L. de; Silva,José Alberto Gonçalves da
Fonte: Academia Brasileira de Neurologia - ABNEURO Publicador: Academia Brasileira de Neurologia - ABNEURO
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/06/2004 Português
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66.825547%
OBJECTIVE: The aim of this study was to evaluate lipoprotein(a) (Lp(a)), total cholesterol, high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), very low density lipoprotein cholesterol (VLDL ), triglycerides , apolipoprotein A (apo A) and B100 (apo B100), uric acid, glycaemic and insulin plasmatic concentrations in patients affected by acute stroke. In this group of patients, we have compared the variables between type 2 diabetic patients and non-diabetic patients. METHOD: We evaluate a total of 34 non-diabetic patients (22 males and 12 females; mean age 66.71 ± 10.83 years) and a group of 26 type 2 diabetic patients (15 males and 11 females; mean age 66.35 ± 9.92 years) in a cross-sectional study. RESULTS: Mean Lp(a) concentration did not significantly differ between type 2 diabetic patients and non-diabetic subjects (29.49 ± 23.09 vs 44.81 ± 44.34 mg/dl). The distribution of Lp(a)levels was highly skewed towards the higher levels in both groups, being over 30 mg/dl in 50%. Lp(a) concentration was positively correlated with abdominal adiposity, using waist-hip ratio(WHR)(p< 0.05). No association was found between Lp(a) and others risk factors like sex, age, other lipidic parameters and the presence of stroke. CONCLUSIONS: Our results showed that there were no significant differences between diabetic and non-diabetic patients' serum Lp(a) levels...

‣ Variation in lipoprotein(a) concentrations among individuals with the same apolipoprotein (a) isoform is determined by the rate of lipoprotein(a) production.

Rader, D J; Cain, W; Zech, L A; Usher, D; Brewer, H B
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /02/1993 Português
Relevância na Pesquisa
56.699985%
Lipoprotein(a) [Lp(a)] is an atherogenic lipoprotein which is similar in structure to, but metabolically distinct from, LDL. Factors regulating plasma concentrations of Lp(a) are poorly understood. Apo(a), the protein that distinguishes Lp(a) from LDL, is highly polymorphic, and apo(a) size is inversely correlated with plasma Lp(a) level. Even within the same apo(a) isoform class, however, plasma Lp(a) concentrations vary widely. A series of in vivo kinetic studies were performed using purified radiolabeled Lp(a) in individuals with the same apo(a) isoform but different Lp(a) levels. In a group of seven subjects with a single S4-apo(a) isoform and Lp(a) levels ranging from 1 to 13.2 mg/dl, the fractional catabolic rate (FCR) of 131I-labeled S2-Lp(a) (mean 0.328 day-1) was not correlated with the plasma Lp(a) level (r = -0.346, P = 0.45). In two S4-apo(a) subjects with a 10-fold difference in Lp(a) level, the FCR's of 125I-labeled S4-Lp(a) were very similar in both subjects and not substantially different from the FCRs of 131I-S2-Lp(a) in the same subjects. In four subjects with a single S2-apo(a) isoform and Lp(a) levels ranging from 9.4 to 91 mg/dl, Lp(a) concentration was highly correlated with Lp(a) production rate (r = 0.993, P = 0.007)...

‣ Lipoprotein(a) and the risk of vascular disease

Erqou, Sebhat
Fonte: Journal of the American Medical Association; Nature Reviews Cardiology; Archives of Internal Medicine; European Journal of Epidemiology; Journal American College of Cardiology; University of Cambridge; Institute of Public Health Publicador: Journal of the American Medical Association; Nature Reviews Cardiology; Archives of Internal Medicine; European Journal of Epidemiology; Journal American College of Cardiology; University of Cambridge; Institute of Public Health
Tipo: Thesis; not applicable; doctoral; PhD
Português
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Background: Lipoprotein(a) [Lp(a)] is composed of a low density-lipoprotein (LDL) particle and a glycoprotein molecule known as apolipoprotein(a) [apo(a)]. Apo(a) exists in several differently-sized isoforms and is responsible for the unique properties of Lp(a). Although Lp(a) has been known for the past 40 years its relationship with coronary heart disease (CHD) has not been characterized in sufficient detail. Whether Lp(a) causes CHD is not clear. Furthermore, the role of apo(a) isoform variation and other sources of Lp(a) heterogeneity (e.g., level of oxidized phospholipids) in Lp(a)-disease association has not been determined. Objectives: To characterize in detail the association of circulating Lp(a) levels with the risk CHD To assess the nature of Lp(a)-CHD association using an integrative genetic study To explore the role of Lp(a) heterogeneity in its association with CHD Data sources: 1. The Emerging Risk Factors Collaboration (ERFC) database (36 studies, 127,000 participants) 2. The European Prospective Investigation of Cancer ? Norfolk (EPIC-Norfolk) study (2200CHD cases, 2200 controls) 3. The Pakistani Risk of Myocardial Infarction Study (PROMIS) (1800 MI cases and 1800 controls) 4. Systematic quantitative reviews of published epidemiological studies Results: ERFC data - Analyses of cross-sectional data on up to 127...