Arteriosclerosis and thrombosis : a journal of vascular biology最新文献

{"title":"The insulin resistance syndrome in smokers is related to smoking habits.","authors":"B Eliasson,&nbsp;S Attvall,&nbsp;M R Taskinen,&nbsp;U Smith","doi":"10.1161/01.atv.14.12.1946","DOIUrl":"https://doi.org/10.1161/01.atv.14.12.1946","url":null,"abstract":"<p><p>The relationship between smoking habits, insulin resistance, and related risk factors for cardiovascular disease was examined in 57 middle-aged male smokers whose degree of insulin resistance was quantified by using the euglycemic clamp technique. Smoking habits correlated with degree of insulin resistance and consequently with various manifestations of the insulin resistance syndrome including levels of insulin, high-density lipoprotein cholesterol, triglycerides, and plasminogen activator inhibitor-1 (PAI-1) activity. Smoking habits, independent of degree of insulin resistance, were also related to levels of total cholesterol and low-density lipoprotein cholesterol as well as triglycerides. Stepwise regression analyses considering the effects of age, lean body mass, body fat, body mass index, waist/hip ratio, and alcohol consumption showed that only smoking habits and percent body fat were independently related to degree of insulin resistance. This study shows that insulin resistance and the insulin resistance syndrome are important but not unique contributors to the strong risk profile for cardiovascular disease in middle-aged men who smoke.</p>","PeriodicalId":8408,"journal":{"name":"Arteriosclerosis and thrombosis : a journal of vascular biology","volume":"14 12","pages":"1946-50"},"PeriodicalIF":0.0,"publicationDate":"1994-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/01.atv.14.12.1946","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18975179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"13C-NMR spectroscopy of human atherosclerotic lesions. Relation between fatty acid saturation, cholesteryl ester content, and luminal obstruction.","authors":"J F Toussaint,&nbsp;J F Southern,&nbsp;V Fuster,&nbsp;H L Kantor","doi":"10.1161/01.atv.14.12.1951","DOIUrl":"https://doi.org/10.1161/01.atv.14.12.1951","url":null,"abstract":"<p><p>Previous investigations have used 13C-nuclear magnetic resonance (NMR) spectroscopy to demonstrate the similarities between lipoproteins and the mobile lipids of atheroma. In this study, we tested the hypothesis that 13C-NMR changes are related to indices of histological severity. We classified 20 human arteries according to their obstruction ratio (OR), defined as the ratio of the plaque area to the area delimited by the external elastic lamina. In group A, OR was < 40%, and in group B, OR was > 40%. We analyzed at 9.4 T the resonances of unsaturated (UFA) and polyunsaturated (PUFA) carbons, the resonances of the carbons 19 and 21 (C19, C21) of cholesteryl esters (CE), the methine carbon peak of fatty acids (CH2)n, the choline peak from phospholipids (PL), and the glycerol peak from triglyceride (TG). The UFA/PUFA, UFA/(CH2)n, and PUFA/(CH2)n ratios are markers of fatty acid saturation. (C19, C21)/(CH2)n, choline/(CH2)n, and glycerol/(CH2)n are indices of CE, PL, and TG content, respectively. UFA/PUFA in group A is 1.15 +/- 0.34 versus 1.63 +/- 0.32 in group B (P = .005). PUFA/(CH2)n is 0.26 +/- 0.10 in group A versus 0.16 +/- 0.04 in group B (P = .049). C19, C21/(CH2)n in group A is 0.32 +/- 0.15 versus 0.63 +/- 0.23 for group B (P = .003). No significant difference was found in UFA/(CH2)n or in the TG or PL ratios. 13C spectral examination of human atherosclerosis demonstrates decreased resonances for polyunsaturated fatty acyl chains and cholesteryl esters with increasing obstruction.</p>","PeriodicalId":8408,"journal":{"name":"Arteriosclerosis and thrombosis : a journal of vascular biology","volume":"14 12","pages":"1951-7"},"PeriodicalIF":0.0,"publicationDate":"1994-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/01.atv.14.12.1951","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18975180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term induction and regression of diet-induced atherosclerotic lesions in rhesus monkeys. II. Morphometric evaluation of lesions by light microscopy in coronary and carotid arteries.","authors":"J P Strong,&nbsp;A K Bhattacharyya,&nbsp;D A Eggen,&nbsp;H C Stary,&nbsp;G T Malcom,&nbsp;W P Newman,&nbsp;C Restrepo","doi":"10.1161/01.atv.14.12.2007","DOIUrl":"https://doi.org/10.1161/01.atv.14.12.2007","url":null,"abstract":"Atherosclerotic lesions were induced in rhesus monkeys (Macaca mulatta) by feeding them a high-saturated fatty acid and high-cholesterol diet. After 5.4 years the extent of lesions in three major coronary arteries and the right carotid artery was evaluated morphometrically by light microscopy in one group of animals (group P). The remaining animals were switched to a low-cholesterol diet that remained high in saturated fatty acids and provided the same percentage of total calories as did the atherogenic diet. Lesion regression was then evaluated in one group of monkeys 1.9 years (group R4) and in another group of monkeys 3.7 years (group R5) after withdrawal of cholesterol alone from the diet. In group P, the mean intimal thickness varied between 26 and 47 microns, maximum intimal thickness between 70 and 92 microns, and luminal reduction between 9% and 12% in the three major coronary arteries. Luminal reduction varied between 1% and 11% in right carotid artery segments. After 1.9 years of consuming the basal diet, group R4 animals were no different from group P animals with respect to morphometric measures. Total intimal and medial areas of the left anterior descending (LAD) coronary artery in groups P and R4 were also similar. In contrast, after 3.7 years of consuming the basal diet, group R5 animals showed consistently although not statistically significantly lower values than those in group P for the morphometric measures in coronary arteries and total intimal area in the LAD. Similar results were obtained for the common carotid and external carotid arteries. Thus, our study shows that long-term diet-induced lesions in coronary arteries and in common and external segments of the right carotid artery regressed only when the animals were fed the basal diet for 3.7 years. We conclude that atherosclerotic lesions induced in coronary and carotid arteries can regress toward normal to a certain extent, but they require a longer time for regression than do other arterial segments. These findings support the results of clinical trials in human subjects.","PeriodicalId":8408,"journal":{"name":"Arteriosclerosis and thrombosis : a journal of vascular biology","volume":"14 12","pages":"2007-16"},"PeriodicalIF":0.0,"publicationDate":"1994-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/01.atv.14.12.2007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18980249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective inhibition of platelet macroaggregate formation by a recombinant heparin-binding domain of human thrombospondin.","authors":"C Legrand,&nbsp;V Morandi,&nbsp;S Mendelovitz,&nbsp;H Shaked,&nbsp;J R Hartman,&nbsp;A Panet","doi":"10.1161/01.atv.14.11.1784","DOIUrl":"https://doi.org/10.1161/01.atv.14.11.1784","url":null,"abstract":"<p><p>Thrombospondin (TSP) is a platelet alpha-granule adhesive protein that plays a critical role in the stabilization of thrombus by promoting the formation of platelet macroaggregates. We have recently shown that a monoclonal antibody (mAb) to the NH2-terminal heparin-binding domain of TSP, MAII, inhibits platelet aggregation induced by thrombin in a dose-dependent manner. In this study, we have expressed in Escherichia coli two recombinant proteins comprising residues 1 to 174 (TSP18) and 1 to 242 (TSP28) of TSP. After purification, both proteins reacted equally well with mAb MAII, whereas the reactivity of TSP18 for heparin was lower than that of TSP28 or native TSP. At micromolar concentrations, TSP18 and TSP28 inhibited the second wave of platelet aggregation and the concomitant release of [14C]5-hydroxytryptamine induced by ADP in citrated platelet-rich plasma as well as aggregation and secretion induced by a low concentration of thrombin in washed platelet suspensions. The proteins did not inhibit surface expression of endogenous TSP on activated platelets, as measured by the binding of radiolabeled mAb 5G11, indicating that they did not interfere with the primary binding of TSP to the plasma membrane. In contrast, in a solid-phase binding assay, the proteins inhibited in a dose-dependent manner (IC50, 0.1 and 0.06 mumol/L for TSP18 and TSP28, respectively) the binding of radiolabeled TSP to surface-adsorbed fibrinogen. Furthermore, specific and saturable binding of the proteins to immobilized fibrinogen was demonstrated by enzyme-linked immunosorbent assay. The results suggest that interaction between the heparin-binding domain of TSP and membrane-bound fibrinogen may be critical in the platelet aggregation/secretion process.</p>","PeriodicalId":8408,"journal":{"name":"Arteriosclerosis and thrombosis : a journal of vascular biology","volume":"14 11","pages":"1784-91"},"PeriodicalIF":0.0,"publicationDate":"1994-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/01.atv.14.11.1784","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18943623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of endotoxin and cytokines on lipoprotein lipase activity in mice.","authors":"K R Feingold,&nbsp;M Marshall,&nbsp;R Gulli,&nbsp;A H Moser,&nbsp;C Grunfeld","doi":"10.1161/01.atv.14.11.1866","DOIUrl":"https://doi.org/10.1161/01.atv.14.11.1866","url":null,"abstract":"<p><p>Endotoxin (lipopolysaccharide [LPS]) stimulates the production of cytokines, which mediate many of the metabolic effects associated with infection. In LPS-sensitive C57B1/6 mice, LPS doses as low as 0.01 micrograms per mouse decreased adipose tissue lipoprotein lipase (LPL) activity by greater than 50%. In LPS-resistant C3H/HeJ mice, which do not produce cytokines in response to LPS, doses of LPS as high as 10 micrograms per mouse did not affect LPL activity in adipose tissue. In muscle of C57Bl/6 mice, LPL activity was decreased by 27% after 10 micrograms of LPS, whereas in C3H/HeJ mice there was no effect. These results indicate that the LPS-induced decrease in both adipose and muscle LPL activity is mediated by cytokines. Tumor necrosis factor (TNF), interleukin (IL)-1, leukemia-inhibiting factor (LIF), interferon alfa, and interferon gamma all decreased adipose tissue LPL activity in intact mice. In skeletal and cardiac muscle, only IL-1 and interferon gamma decreased LPL activity, whereas TNF, LIF, and interferon alfa had no effect. Inhibition of TNF activity blocked the increase in serum triglycerides that is characteristically observed after LPS but did not affect the ability of LPS to decrease adipose tissue LPL activity. Inhibition of IL-1 activity with IL-1 receptor antagonist partially inhibited the increase in serum triglycerides; however, the ability of LPS to decrease LPL activity in either adipose or muscle tissue was not affected. These data indicate that although TNF and IL-1 play a role in mediating the increase in serum triglyceride levels, these cytokines do not play a crucial role in the inhibition of either adipose or muscle LPL activity.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":8408,"journal":{"name":"Arteriosclerosis and thrombosis : a journal of vascular biology","volume":"14 11","pages":"1866-72"},"PeriodicalIF":0.0,"publicationDate":"1994-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/01.atv.14.11.1866","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18945365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased radiosensitivity and radioresistant DNA synthesis in cultured fibroblasts from patients with coronary atherosclerosis.","authors":"M A Hannan,&nbsp;F Khougeer,&nbsp;Z Halees,&nbsp;A M Sanei,&nbsp;B A Khan","doi":"10.1161/01.atv.14.11.1761","DOIUrl":"https://doi.org/10.1161/01.atv.14.11.1761","url":null,"abstract":"<p><p>Cultured skin fibroblasts from five patients with atherosclerosis who underwent coronary artery bypass graft surgery were compared with those from one ataxia telangiectasia (AT) homozygote, three AT heterozygotes, and five healthy subjects to determine their sensitivity to gamma radiation as determined by a colony survival assay. Fibroblasts from four of these patients were also compared with those from two AT homozygotes, two AT heterozygotes, and three healthy subjects to determine postirradiation [3H]thymidine incorporation, indicating the levels of radioresistant DNA synthesis (RDS). On the basis of colony survival assay, after long-term irradiation (at low dose rate, ie, 0.007 Gy/min), fibroblasts from all five patients with atherosclerosis exhibited radiosensitivity that was intermediate between that of the healthy subjects and that of patients with the known radiosensitive syndrome AT. However, there was a considerable interstrain difference in the radiosensitivity of fibroblasts from patients with atherosclerosis, with their mean D10 values (radiation dose resulting in 10% cell survival) varying between 2.3 and 6.2 Gy, whereas the mean D10 values for the cells from the AT homozygote, AT heterozygotes, and healthy subjects were 2.0, 3.8, and 9.0 Gy, respectively. One of the patients with atherosclerosis showed cellular radiosensitivity quite similar to that of the AT homozygote, up to 2% to 10% of survival levels after short- (at a dose rate of 8 Gy/min) and long-term irradiation, respectively. The results of [3H]thymidine incorporation showed an AT heterozygote-like RDS in fibroblasts from patients with atherosclerosis that appeared to be intermediate between that of AT homozygotes and that of healthy subjects, suggesting a partial deregulation of cell cycle in the patients with atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":8408,"journal":{"name":"Arteriosclerosis and thrombosis : a journal of vascular biology","volume":"14 11","pages":"1761-6"},"PeriodicalIF":0.0,"publicationDate":"1994-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/01.atv.14.11.1761","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18943620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Triglyceride-rich lipoproteins isolated by selected-affinity anti-apolipoprotein B immunosorption from human atherosclerotic plaque.","authors":"J H Rapp,&nbsp;A Lespine,&nbsp;R L Hamilton,&nbsp;N Colyvas,&nbsp;A H Chaumeton,&nbsp;J Tweedie-Hardman,&nbsp;L Kotite,&nbsp;S T Kunitake,&nbsp;R J Havel,&nbsp;J P Kane","doi":"10.1161/01.atv.14.11.1767","DOIUrl":"https://doi.org/10.1161/01.atv.14.11.1767","url":null,"abstract":"<p><p>We isolated and characterized immunoreactive apolipoprotein B (apoB)-containing lipoproteins from human atherosclerotic plaque and plasma to determine whether very-low-density lipoprotein (VLDL) can enter and become incorporated into the atherosclerotic lesion and how plaque apoB-containing lipoproteins differ from apoB-containing lipoproteins isolated from plasma. Atherosclerotic plaques were obtained during aortic surgery and processed immediately. Lipoproteins were extracted from minced plaque in a buffered saline solution (extract A). In selected cases a second extraction was done after plaque was incubated with collagenase (extract B). Lipoproteins were then isolated from the extracts by anti-apoB immunosorption and separated into VLDL + intermediate-density lipoprotein (IDL) (d < 1.019 g/mL) and low-density lipoprotein (LDL) (1.019 < d < 1.070 g/mL) fractions by ultracentrifugation. The VLDL + IDL fractions from plaque contained more than one third of the total apoB-associated lipoprotein cholesterol in both extracts A and B. The lipid composition of VLDL + IDL in both extracts was related to that of plasma VLDL + IDL. By electron microscopy mean particle diameters of VLDL + IDL from extracts A and B were 9% and 23%, respectively, greater than VLDL + IDL diameters from plasma. Mean diameters of LDL from extracts A and B were 11% and 31% greater than LDL diameters from plasma. The apoE-apoB ratio of extract A VLDL + IDL was nearly twice that of plasma VLDL + IDL and severalfold higher than that of extract A LDL. Immunoblots of both VLDL + IDL and LDL from extract A demonstrated minimal fragmentation of apoB.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":8408,"journal":{"name":"Arteriosclerosis and thrombosis : a journal of vascular biology","volume":"14 11","pages":"1767-74"},"PeriodicalIF":0.0,"publicationDate":"1994-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/01.atv.14.11.1767","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18943621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysbetalipoproteinemia in a kindred with hypobetalipoproteinemia due to mutations in the genes for ApoB (ApoB-70.5) and ApoE (ApoE2).","authors":"W A Groenewegen,&nbsp;E S Krul,&nbsp;M R Averna,&nbsp;J Pulai,&nbsp;G Schonfeld","doi":"10.1161/01.atv.14.11.1695","DOIUrl":"https://doi.org/10.1161/01.atv.14.11.1695","url":null,"abstract":"<p><p>We identified the first insertion mutation that specifies an apolipoprotein (apo)B truncation, apoB-70.5, in a father and son with hypobetalipoproteinemia (total and low-density lipoprotein [LDL] cholesterol < 5th percentile, plasma apoB levels approximately one third of normal). The mutation is due to insertion of an adenine (A) into a 7-A repeat between cDNA position 9754 and 9760 of the apoB gene, resulting in a frame shift of 13 new amino acids and a termination codon at amino acid residue 3197. The DNA mutation cosegregated with the apoB truncation and hypobetalipoproteinemia in the kindred. The two apoB-70.5/apoB-100 heterozygotes also are apoE2 homozygotes by genotyping; beta-very-low-density lipoprotein (VLDL) was present, and VLDL cholesterol/triglyceride ratios were increased (0.29) in the plasmas of both. Density gradient ultracentrifugation and gel filtration chromatography profiles showed increased amounts of particles in the VLDL and intermediate-density lipoprotein density and size ranges and relatively smaller peaks of LDL than in controls. Two populations of LDL were present, ApoB-70.5 was primarily associated with LDL particles of higher density and of smaller size than the LDL particles containing apoB-100. ApoB-48-containing particles were present in the VLDL of fasting plasmas of both subjects, and the postprandial levels of chylomicrons and remnants as measured by the vitamin A fat tolerance test were increased. In conclusion, both subjects heterozygous for apoB-70.5 and homozygous for apoE2 showed the classic characteristics of dysbetalipoproteinemia superimposed onto the hypolipoproteinemia state.</p>","PeriodicalId":8408,"journal":{"name":"Arteriosclerosis and thrombosis : a journal of vascular biology","volume":"14 11","pages":"1695-704"},"PeriodicalIF":0.0,"publicationDate":"1994-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/01.atv.14.11.1695","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18943696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HDL and apolipoprotein A-I protect erythrocytes against the generation of procoagulant activity.","authors":"R M Epand,&nbsp;A Stafford,&nbsp;B Leon,&nbsp;P E Lock,&nbsp;E M Tytler,&nbsp;J P Segrest,&nbsp;G M Anantharamaiah","doi":"10.1161/01.atv.14.11.1775","DOIUrl":"https://doi.org/10.1161/01.atv.14.11.1775","url":null,"abstract":"<p><p>The appearance of anionic lipids on the extracellular surface of cells is required for the formation of the procoagulant complex that leads to the activation of prothrombin. Procoagulant activity would be expected to be inhibited by substances that stabilize the membrane structure and hence inhibit the transbilayer diffusion of phosphatidylserine from the cytoplasmic to the extracellular surface of the plasma membrane. The generation of procoagulant activity in human erythrocytes by A23187 and Ca2+ is inhibited by apolipoprotein A-I, its amphipathic peptide analogues, and high-density lipoprotein (HDL). These agents do not inhibit the Ca2+ loading of erythrocytes by A23187, nor do they inhibit the activation of prothrombin once the cells have been incubated at 37 degrees C with A23187 and Ca2+. Transbilayer diffusion of fluorescently labeled phosphatidylserine is inhibited by apolipoprotein A-I. These findings indicate that class A amphipathic helixes as well as lipoprotein particles and liposomes inhibit the transbilayer diffusion of phospholipids and procoagulant activity. This activity may contribute to the protective role of HDL against arteriosclerosis and thrombosis.</p>","PeriodicalId":8408,"journal":{"name":"Arteriosclerosis and thrombosis : a journal of vascular biology","volume":"14 11","pages":"1775-83"},"PeriodicalIF":0.0,"publicationDate":"1994-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/01.atv.14.11.1775","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18943622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Binding of recombinant apolipoprotein(a) to extracellular matrix proteins.","authors":"Y Y van der Hoek,&nbsp;W Sangrar,&nbsp;G P Côté,&nbsp;J J Kastelein,&nbsp;M L Koschinsky","doi":"10.1161/01.atv.14.11.1792","DOIUrl":"https://doi.org/10.1161/01.atv.14.11.1792","url":null,"abstract":"<p><p>Elevated levels of lipoprotein(a), which consists of apolipoprotein(a) [apo(a)] covalently linked to a low-density lipoprotein-like moiety, is an independent risk factor for the development of atherosclerosis. We show that a recombinant form of apo(a) [r-apo(a)] binds strongly to fibronectin and fibrinogen, weakly to laminin, and not at all to von Willebrand factor, vitronectin, or collagen type IV. In contrast to the binding of plasminogen to fibronectin, r-apo(a) binding does not appear to be mediated by lysine-dependent interactions, based on the inability of epsilon-aminocaproic acid concentrations up to 0.2 mol/L to significantly decrease r-apo(a) binding to fibronectin. Plasminogen competed weakly for the binding of r-apo(a) to fibronectin, whereas r-apo(a) completely abolished plasminogen binding. The 29- and 38-kd heparin-binding thermolysin fragments of fibronectin, previously identified as the lipoprotein(a) binding domains, were digested with trypsin, and a peptide that retained the ability to bind r-apo(a) was isolated; the sequence of the peptide (AVTTIPAPTDLK) corresponds to the amino terminus of the 29- and 38-kd domains. A synthetic peptide with this sequence was able to compete effectively with fibronectin for r-apo(a) binding.</p>","PeriodicalId":8408,"journal":{"name":"Arteriosclerosis and thrombosis : a journal of vascular biology","volume":"14 11","pages":"1792-8"},"PeriodicalIF":0.0,"publicationDate":"1994-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/01.atv.14.11.1792","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18943624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}