Browsing by Subject "Lipoproteins"

Now showing 1 - 6 of 6
  • Thumbnail Image
    Item
    Open Access
    Anti-retroviral therapy increases the prevalence of dyslipidemia in South African HIV-infected patients
    (Public Library of Science, 2016) Dave, Joel A; Levitt, Naomi S; Ross, Ian L; Lacerda, Miguel; Maartens, Gary; Blom, Dirk
    Purpose Data on the prevalence of dyslipidaemia and associated risk factors in HIV-infected patients from sub-Saharan Africa is sparse. We performed a cross-sectional analysis in a cohort of HIV-infected South African adults. METHODS: We studied HIV-infected patients who were either antiretroviral therapy (ART)-naive or receiving non-nucleoside reverse transcriptase inhibitor (NNRTI)-based or protease inhibitor (PI)-based ART. Evaluation included fasting lipograms, oral glucose tolerance tests and clinical anthropometry. Dyslipidemia was defined using the NCEP ATPIII guidelines. RESULTS: The median age of the participants was 34 years (range 19-68 years) and 78% were women. The prevalence of dyslipidemia in 406 ART-naive and 551 participants on ART was 90.0% and 85%, respectively. Low HDL-cholesterol (HDLC) was the most common abnormality [290/406 (71%) ART-naïve and 237/551 (43%) ART- participants]. Participants on ART had higher triglycerides (TG), total cholesterol (TC), LDL-cholesterol (LDLC) and HDLC than the ART-naïve group. Severe dyslipidaemia, (LDLC> 4.9 mmol/L or TG >5.0 mmol/L) was present in <5% of participants. In multivariate analyses there were complex associations between age, gender, type and duration of ART and body composition and LDLC, HDLC and TG, which differed between ART-naïve and ART-participants. CONCLUSION: Participants on ART had higher TG, TC, LDLC and HDLC than those who were ART-naïve but severe lipid abnormalities requiring evaluation and treatment were uncommon.
  • Thumbnail Image
    Item
    Open Access
    The cellular degradation of the low density lipoprotein receptor and its ligand
    (1987) Casciola, Livia Angela Flavia; Coetzee, G A
    The cellular degradation of the low density lipoprotein (LDL) receptor, and its ligand, LDL, were investigated in order to clarify certain mechanistic aspects of these important processes. Long-term lymphoblastoid cell lines and cultured human skin fibroblasts were used to examine the fate of ¹²⁵I-LDL subsequent to its uptake via receptor-mediated endocytosis. In both cases, binding activity was saturable, depended on the presence of calcium ions in the medium, and was calculated to have an equilibrium dissociation constant at 4ᵒC of 2 μg ¹²⁵I-LDL/ml. No high-affinity binding was detected when the ligand was modified by acetylation. After incubating the monolayers at 37°C LDL/LDL receptor complexes were internalized, and the receptors were recycled back to the surface within about 10 minutes. Apolipo-protein B in the LDL particles was largely degraded to the amino acid level: chloroquine, a lysosomotropic agent, inhibited the formation of the ¹²⁵I-LDL degradation products. Cells obtained from a number of heterozygous and homozygous familial hypercholesterolemic patients, as expected, bound markedly reduced amounts of ligand. The half-life of ¹²⁵I-LDL was measured after it had been introduced into cultured fibroblasts by one of the following processes: (i) uptake via receptor-mediated endocytosis in human skin fibroblasts with normal LDL receptors, or (ii) incorporation via scrape-loading into fibroblasts defective in LDL receptor content. The half-lives obtained were about 1 hour and 50 hours, respectively, indicating that efficient degradation of LDL occurred only when it was deIivered to lysosomes via receptor-mediated endocytosis.
  • Thumbnail Image
    Item
    Open Access
    The expression and metabolism of low density lipoprotein receptors in familial hypercholesterolaemia
    (1989) Fourie, Anne Madeleine; Van der Westhuyzen, Deneys R
    The expression of two phenotypically-contrasting LDL receptor mutations was characterized in cultured fibroblasts from the genetically-homozygous Afrikaner subjects, FH1a and lb, and FH3a and 3b, respectively. Surface receptor expression and functional activity were studied by ligand (¹²⁵I-LDL) and monoclonal antibody (¹²⁵I-IgG-C7) binding, and c35s]-methionine pulse-chase experiments were used to analyze biosynthesis, processing and degradation of IgG-C7- immunoprecipitable mutant receptors. Cells from the "receptor-negative" subjects, FH3a and 3b exhibited reduced, but significant (40-60% of normal) LDL receptor synthesis rates. Newly-synthesized precursors were processed slowly (t½ 1.5 hours versus normal t½ of approximately 15 minutes) to mature receptors which reached the cell-surface, but were rapidly degraded thereafter with a half-life of approximately 1.7 hours (normal value 12.6 hours) thus representing a new type of LDL receptor defect. Lysosomotropic weak bases such as ammonium chloride partially inhibited rapid degradation of the mutant receptors, suggesting the involvement of proteolysis in acidic compartments such as lysosomes or endosomes. Fibroblasts from FH1a and lb exhibited normal synthesis rates of LDL receptor precursors that were processed at a severely reduced rate (t½ approximately 5 hours) to functionally heterogeneous mature surface receptors. Onethird of the receptors (20% of normal levels) bound ¹²⁵I-LDL with normal affinity at 4°C and 37°C, whereas the majority were able to recognize only ¹²⁵I-IgG-C7, and apparently showed defective internalisation and subsequent degradation of the bound IgG-C7 at 37°C. The existence of the two receptor populations was further supported by selective intracellular trapping and degradation of only the active, LDL-binding population, in the presence of ammonium chloride and LOL. The abnormal form predominated even in newly-synthesized receptors and reached a maximum of 50-70% of normal levels after 48 hours of upregulation. Upregulation kinetics and degradation rates (t½ = 10-11 hours) of both functionally-active and abnormal receptor populations were similar to normal. A progressive increase in apparent molecular weight of the slowly-processed precursor receptors suggested a possible role for abnormal glycosylation in the formation of both "normal" and abnormal conformations of the same receptor molecule.
  • Thumbnail Image
    Item
    Open Access
    Lipoprotein lipase activity is decreased in a large cohort of patients with coronary artery disease and is associated with changes in lipids and lipoproteins
    (1999) Hockman, Dorit; Henderson,Howard E; Hockman, Dorit; Kastelein, John P; Zwinderman, Aeilko H; Gagné, Eric; Jukema, J Wouter; Reymer, Paul W A; Groenemeyer, Björn E; Hockman, Dorit; Lie, Kong I; Bruschke, Albert V G; Hayden, Michael R; Jansen, Hans
    Lipoprotein lipase (LPL) is crucial in the hydrolysis of triglycerides (TG) in TG-rich lipoproteins in the formation of HDL particles. As both these lipoproteins play an important role in the pathogenesis of atherosclerotic vascular disease, we sought to assess the relationship between post-heparin LPL (PH-LPL) activity and lipids and lipoproteins in a large, well-defined cohort of Dutch males with coronary artery disease (CAD). These subjects were drawn from the REGRESS study, totaled 730 in number and were evaluated against 75 healthy, normolipidemic male controls. Fasting mean PH-LPL activity in the CAD subjects was 108 46 mU/ml, compared to 138 44 mU/ml in controls (P < 0.0001). When these patients were divided into activity quartiles, those in the lowest versus the highest quartile had higher levels of TG (P < 0.001), VLDLc and VLDL-TG (P = 0.001). Conversely, levels of TC, LDL, and HDLc were lower in these patients (P = 0.001, P = 0.02, and P = 0.001, respectively). Also, in this cohort PH-LPL relationships with lipids and lipoproteins were not altered by apoE genotypes. The frequency of common mutations in the LPL gene associated with partial LPL deficiency (N291S and D9N carriers) in the lowest quartile for LPL activity was more than double the frequency in the highest quartile (12.0% vs. 5.0%; P = 0.006). By contrast, the frequency of the S447X LPL variant rose from 11.5% in the lowest to 18.3% (P = 0.006) in the highest quartile. This study, in a large cohort of CAD patients, has shown that PH-LPL activity is decreased (22%; P = 0.001) when compared to controls; that the D9N and N291S, and S447X LPL variants are genetic determinants, respectively, in CAD patients of low and high LPL PH-LPL activities; and that PH-LPL activity is strongly associated with changes in lipids and lipoproteins.
  • Thumbnail Image
    Item
    Open Access
    Lipoprotein metabolism and its derangements
    (2003) Marais, David
    The purpose of this article is to provide the medical practitioner with an understanding of lipids, lipoproteins and their metabolism and disorders. Such an understanding would enhance the assimilation of the sections on clinical assessment and treatment of dyslipoproteinaemia. Lipids may be defined as organic chemicals that are insoluble in water. In the biological context lipids are either carboxylic acids (fatty acids) or sterols, and their derivatives. Lipids are less dense than water and will float spontaneously or under centrifugal force. Cholesterol is the principal sterol in the animal kingdom and promotes the impenetrability of the phospholipid bilayer that constitutes the cell membrane. Additionally cholesterol is found in lipoproteins and in bile and is used to synthesise hormones and bile acids.
  • Thumbnail Image
    Item
    Open Access
    Rising diabetes prevalence among urban-dwelling black South Africans
    (Public Library of Science, 2012) Peer, Nasheeta; Steyn, Krisela; Lombard, Carl; Lambert, Estelle V; Vythilingum, Bavanisha; Levitt, Naomi S
    Objective: To examine the prevalence of and the association of psychosocial risk factors with diabetes in 25-74-year-old black Africans in Cape Town in 2008/09 and to compare the prevalence with a 1990 study. Research Design and METHODS: A randomly selected cross-sectional sample had oral glucose tolerance tests. The prevalence of diabetes (1998 WHO criteria), other cardiovascular risk factors and psychosocial measures, including sense of coherence (SOC), locus of control and adverse life events, were determined. The comparison of diabetes prevalence between this and a 1990 study used the 1985 WHO diabetes criteria. RESULTS: There were 1099 participants, 392 men and 707 women (response rate 86%). The age-standardised (SEGI) prevalence of diabetes was 13.1% (95% confidence interval (CI) 11.0-15.1), impaired glucose tolerance (IGT) 11.2% (9.2-13.1) and impaired fasting glycaemia 1.2% (0.6-1.9). Diabetes prevalence peaked in 65-74-year-olds (38.6%). Among diabetic participants, 57.9% were known and 38.6% treated. Using 1985 WHO criteria, age-standardised diabetes prevalence was higher by 53% in 2008/09 (12.2% (10.2-14.2)) compared to 1990 (8.0% (5.8-10.3)) and IGT by 67% (2008/09: 11.7% (9.8-13.7); 1990: 7.0% (4.9-9.1)). In women, older age (OR: 1.05, 95%CI: 1.03-1.08, p<0.001), diabetes family history (OR: 3.13, 95%CI: 1.92-5.12, p<0.001), higher BMI (OR: 1.44, 95%CI: 1.20-1.82, p = 0.001), better quality housing (OR: 2.08, 95%CI: 1.01-3.04, p = 0.047) and a lower SOC score (≤40) was positively associated with diabetes (OR: 2.57, 95%CI: 1.37-4.80, p = 0.003). Diabetes was not associated with the other psychosocial measures in women or with any psychosocial measure in men. Only older age (OR: 1.05, 95%CI: 1.02-1.08, p = 0.002) and higher BMI (OR: 1.10, 95%CI: 1.04-1.18, p = 0.003) were significantly associated with diabetes in men. CONCLUSIONS: The current high prevalence of diabetes in urban-dwelling South Africans, and the likelihood of further rises given the high rates of IGT and obesity, is concerning. Multi-facetted diabetes prevention strategies are essential to address this burden.