K Horita, M Eto, M Saito, H Nakata, Y Iwashima, H Ito, M Takahashi, A Kondo, A Morikawa, I Makino
{"title":"Effects of apolipoprotein E polymorphism on plasma lipoprotein(a) levels.","authors":"K Horita, M Eto, M Saito, H Nakata, Y Iwashima, H Ito, M Takahashi, A Kondo, A Morikawa, I Makino","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Effects of apolipoprotein E (apo E) genetic polymorphism on plasma lipoprotein(a) (Lp(a)) levels were investigated in 305 civil service workers (158 men and 147 women). Plasma Lp(a) levels were measured by ELISA. Apo E phenotypes were determined from plasma by isoelectric focusing, Western blotting and immunostaining, as we previously reported. A total of 305 subjects were divided into the three apo E groups; apo E2 group (n = 19 for apo E3/2 and n = 4 for apo E4/2), Apo E3/3 group (n = 224) and apo E4/3 group (n = 58). Mean levels of plasma Lp(a) were 14.2 mg/dl. Plasma Lp(a) levels were significantly lower in the apo E2 group (6.6 mg/dl) than in the apo E3/3 (15.1 mg/dl) and E4/3 (13.7 mg/dl) groups. Plasma total cholesterol (T-chol) and low density lipoprotein (LDL)-chol levels were significantly lower in the apo E2 group than in the apo E4/3 group and tended to be highest in the apo E4/3 group. A significant positive correlation was noted between plasma Lp(a) levels and plasma LDL-chol levels, indicating that the effects of apo E polymorphism on plasma Lp(a) levels were parallel to its effects on plasma LDL-chol levels. In women plasma Lp(a) levels were significantly lower in the apo E2 group than in the apo E3/3 and E4/3 groups, whereas in men plasma Lp(a) levels tended to be lower in the apo E2 group but no significant difference was noted among the three apo E groups. It is concluded that plasma Lp(a) levels are, at least in part, modulated by apo E polymorphism (particularly apo E2) and that there is a gender difference in the effects of apo E polymorphism on plasma Lp(a) levels.</p>","PeriodicalId":75564,"journal":{"name":"Artery","volume":"20 6","pages":"324-36"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19004859","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":"Interactions between cultured bovine arterial endothelial and smooth muscle cells; further studies on the effects of injury and modification of the consequences of injury.","authors":"C B Xu, L Stavenow, H Pessah-Rasmussen","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The hypothesis that cells of the arterial wall might modify the consequences of arterial injury was tested. Bovine aortic endothelial cells (EC) or smooth muscle cells (SMC) were exposed to the two toxic stimuli 3,4-benzo(a)pyrene (BP) and dimethylsulfoxide-soluble particulate matter from cigarette smoke (DSP) or factors released from platelets. The modification of the injury caused by these substances on arterial cells was studied by using a conditioned medium from arterial cells or an EC-SMC co-culture model. Direct addition of BP or DSP to the EC or SMC cultures induced toxic effects on the cells. DSP caused a decreased release of prostacyclin by EC. Conditioned medium from EC and SMC modified these toxic effects, which resulted in a reduced cell death and a further decreased cell proliferation, while conditioned medium from SMC increased the release of prostacyclin by EC injured by DSP. In EC-SMC co-culture the same modifications were obtained. The modification of cell injury was not linked to cell proliferation but instead the results suggested that the effects were mediated by multiple substances released from arterial cells. It is concluded that interactions between different cells in the arterial wall, in the non-injured as well as in the injured state, could be modified by endogeneous substances. This might be of relevance for atherogenesis.</p>","PeriodicalId":75564,"journal":{"name":"Artery","volume":"20 3","pages":"163-79"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19230129","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}
E Koh, S Morimoto, B Jiang, T Inoue, T Nabata, S Kitano, O Yasuda, K Fukuo, T Ogihara
{"title":"Effects of beraprost sodium, a stable analogue of prostacyclin, on hyperplasia, hypertrophy and glycosaminoglycan synthesis of rat aortic smooth muscle cells.","authors":"E Koh, S Morimoto, B Jiang, T Inoue, T Nabata, S Kitano, O Yasuda, K Fukuo, T Ogihara","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The effects of beraprost sodium, a stable analogue of prostacyclin, on the syntheses of DNA, protein and glycosaminoglycans (GAG) of cultured vascular smooth muscle cells (SMC) were studied. SMC were isolated from the thoracic aorta of male Wistar rats. The syntheses of DNA, protein and GAG of SMC were determined by incorporations of [3H]thymidine, [3H]leucine and [35S]sulfuric acid, respectively. Insulin at a concentration of 10(-6) M stimulated DNA synthesis 4 fold compared to control. Beraprost sodium suppressed the insulin-stimulated DNA synthesis dose-dependently at concentrations greater than 10(-7) M and suppressed it by 68% at 10(-5) M. Platelet derived growth factor (PDGF) at a concentration of 20 ng/ml stimulated DNA synthesis 6 fold compared to control. Beraprost sodium suppressed the PDGF-stimulated DNA synthesis dose-dependently at concentrations greater than 10(-7) M and suppressed it by 51% at 10(-5) M. Beraprost sodium suppressed GAG synthesis dose-dependently at concentrations greater than 10(-7) M and suppressed it by 49% at 10(-5) M. However, beraprost sodium at concentrations up to 10(-5) M did not affect protein synthesis. These results indicate that beraprost sodium suppressed the proliferation and GAG synthesis of SMC but did not affect hypertrophy. Beraprost sodium may be a potent antiarteriosclerotic agent through suppression of hyperplasia of SMC and modification of matrix protein.</p>","PeriodicalId":75564,"journal":{"name":"Artery","volume":"20 5","pages":"242-52"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19132688","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}
K Yamada, M Naito, T Hayashi, K Asai, N Yoshimine, A Iguchi
{"title":"Effects of dexamethasone on migration of human monocytes in response to oxidized beta-very low density lipoprotein.","authors":"K Yamada, M Naito, T Hayashi, K Asai, N Yoshimine, A Iguchi","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objective: </strong>We previously showed that dexamethasone inhibited the development of atherosclerosis in cholesterol-fed rabbits. In the present study, we investigated the mechanisms of this inhibition.</p><p><strong>Methods: </strong>Monocytes were isolated from the peripheral blood of healthy donors. Cell suspensions were incubated with dexamethasone, 10(-11)-10(-4)M, for 90 minutes at 37 degrees C. Rabbit beta-very low density lipoprotein(beta-VLDL) was obtained from New Zealand White rabbits that had been fed chow containing 1% cholesterol. Oxidative modification of beta-VLDL was performed by auto-oxidation. We measured the migration of monocytes in response to native and oxidized beta-VLDL using a 48-well microchemotaxis chamber.</p><p><strong>Results: </strong>Oxidized beta-VLDL stimulated the migration of monocytes dose-dependently in the range between 0.5 and 2 nmol/mg protein. Dexamethasone inhibited the chemotaxis of monocytes exposed to oxidized beta-VLDL in a dose-dependent manner more than 10(-9)M.</p><p><strong>Conclusions: </strong>Inhibition of the chemotactic response of monocytes exposed to oxidized beta-VLDL may be a mechanism for the anti-atherogenic effect of dexamethasone in cholesterol-fed rabbits.</p>","PeriodicalId":75564,"journal":{"name":"Artery","volume":"20 5","pages":"253-67"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19132689","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":"Terbutaline-induced desensitization in rabbit aorta in vitro.","authors":"C H Hsu, C P Robinson","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In vivo administration of terbutaline, a beta 2-adrenergic agonist, desensitizes beta-adrenergic agonist-induced responses in isolated rabbit aorta. Characteristics of the desensitization following in vitro application of terbutaline and prevention of such desensitization by certain agents were studied. Endothelium-denuded rabbit aorta rings were incubated with 10 or 50 microM terbutaline for 30 or 60 min, or with no drug as a control. Following contraction with 1 microM phenylephrine, relaxations to cumulative concentrations of isoproterenol were determined. Rings exposed to terbutaline relaxed less to isoproterenol, indicating desensitization of beta-adrenergic receptors. The desensitization was homologous, exposure time- and concentration-dependent, and at least partially reversible. It does not require extracellular calcium to develop and is not blocked by verapamil, ketotifen, prednisolone or nedocromil. Thus, terbutaline-induced desensitization occurs in vitro, is homologous, does not require calcium, and is not blocked by the four compounds tested.</p>","PeriodicalId":75564,"journal":{"name":"Artery","volume":"20 5","pages":"280-302"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19132691","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}
M Naito, T Hayashi, K Yamada, K Asai, N Yoshimine, A Iguchi
{"title":"Protective effects of idebenone on vascular endothelial cells against toxicity induced by oxidatively modified low density lipoprotein.","authors":"M Naito, T Hayashi, K Yamada, K Asai, N Yoshimine, A Iguchi","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We examined the protective effects of idebenone, 6-(10-hydroxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone, on the cytotoxicity of oxidatively-modified low density lipoprotein (oxLDL), using cultured vascular endothelial cells from fetal bovine aorta. When the cells were incubated with idebenone, the toxicity of oxLDL was inhibited dose-dependently (10(-7)-10(-5) M). When cells were preincubated with idebenone, the toxicity of oxLDL was inhibited only at a high concentration (10(-5) M). However, idebenone had no significant effects on copper-induced modification of LDL. The protective effects of idebenone on oxLDL-induced endothelial toxicity may be beneficial for the inhibition of the development of atherosclerosis in the brain and other arterial systems.</p>","PeriodicalId":75564,"journal":{"name":"Artery","volume":"20 6","pages":"314-23"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19004858","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":"Glucose effects on oxygen consumption by the arterial wall.","authors":"H A Massaldi, J L Gainer","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The effect of both D- and L-glucose on the rate of oxygen consumption in rat aorta was determined. Oxygen uptake (V02) was found to decrease when the concentration of D-glucose in the medium was increased, with the same effect being found when L-glucose, rather than D-glucose, was used. Based on these results, it would appear that the decrease in the vascular wall oxygen consumption which results from increased glucose levels is not due to a metabolic effect since one of the isomers (D) is metabolized and the other (L) is not. It is suggested, instead, that these results may be be due to a change in the diffusion of oxygen. Possible implications for atherogenesis are also discussed.</p>","PeriodicalId":75564,"journal":{"name":"Artery","volume":"20 1","pages":"51-60"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19431761","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 cholesterol oxides on prostacyclin production and platelet adhesion.","authors":"S K Peng, B Hu, A Y Peng, R J Morin","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Prostacyclin (PGI2) is synthesized primarily by endothelial cells, is essential for maintenance of vascular integrity, and may play a role in atherogenesis. Human umbilical vein endothelial cells in culture were incubated with either pure cholesterol, 25-hydroxycholesterol, 7-ketocholesterol, cholesterol 5 alpha,6 alpha-epoxide or cholestane-3 beta,5 alpha,6 beta-triol at 10 micrograms/ml culture medium concentration for 12 hours and 24 hours. PGI2 production measured by radioimmunoassay of 6-keto PGF1 alpha, the stable metabolite of PGI2 was inhibited by 39.6%, 27.3%, 40.1% and 31.9% after incubation with 25-hydroxycholesterol, 7-ketocholesterol, cholesterol 5 alpha, 6 alpha-epoxide or cholestane-3 beta,5 alpha,6 beta-triol for 12 hours respectively. Further inhibitory effects were shown after 24 hours of incubation with 25-hydroxycholesterol and 7-ketocholesterol. Platelet adhesion onto endothelial cell monolayers measured by 111In-labeled platelets was enhanced by 104%, 54% and 37% after incubation with cholestane-3 beta, 5 alpha,6 beta-triol, 25-hydroxycholesterol, and 7-ketocholesterol at 10 micrograms/ml concentration for 12 hours respectively. Pure cholesterol at the same concentration had no effect on PGI2 production or platelet adhesion.</p>","PeriodicalId":75564,"journal":{"name":"Artery","volume":"20 3","pages":"122-34"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19229601","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}
M A Rahmani, T Mangroo, M Neves, M Bienaime, S Wiggins, J Williams
{"title":"Effect of aspirin on the contractility of aortic rings in vitro from spontaneously hypertensive rats.","authors":"M A Rahmani, T Mangroo, M Neves, M Bienaime, S Wiggins, J Williams","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The effect of Acetylsalicylic acid (ASA) on the responsiveness of rat aortic smooth muscle was investigated by comparing the contractility of aortic rings from SHR and WKY rats in response to alpha-agonist, phenylephrine (PE). Cumulative dose response curves for PE were generated from aortic rings of SHR and WKY rats in the presence and absence of 0.2mM ASA. To investigate the involvement of endothelium on ASA mediated effects, active tension was recorded for denuded and non-denuded rings from SHR animals in response to KCl and PE. Denuded and non-denuded aortic rings from SHR animals in the presence of ASA produced significantly higher active tension than in the absence of ASA. The reactivity of aortic rings from WKY control animals was not altered significantly in the presence of ASA. These studies suggest that ASA can also modulate aortic contractility through other mechanism(s) in addition to its effect on the metabolites of arachidonic acid. Significance of these observations is discussed below.</p>","PeriodicalId":75564,"journal":{"name":"Artery","volume":"20 3","pages":"135-46"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19229602","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}
Y Homma, T Kobayashi, H Yamaguchi, H Sakane, H Ozawa, M Matsuda, Y Mikami, Y Mikami, H Nakamura
{"title":"Decrease of plasma large, light LDL (LDL1), HDL2 and HDL3 levels with concomitant increase of cholesteryl ester transfer protein (CETP) activity by probucol in type II hyperlipoproteinemia.","authors":"Y Homma, T Kobayashi, H Yamaguchi, H Sakane, H Ozawa, M Matsuda, Y Mikami, Y Mikami, H Nakamura","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The effects of 12 week probucol treatment on plasma lipoprotein subfraction levels and on lecithin: cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) activities in type II hyperlipoproteinemia were investigated. Plasma VLDL-TG, VLDL-apoB, VLDL-apoCII and VLDL-apoCIII concentrations were not changed by probucol, but VLDL-TC and VLDL-PL levels were slightly reduced. Probucol slightly reduced plasma IDL-TC, but not IDL-TG, IDL-PL and IDL-apoB levels. Plasma large, light LDL (LDL1)-TC, LDL1-PL, LDL1-apoB levels were decreased significantly by 28.5 +/- 20.1% (p < 0.001), 18.1 +/- 18.8% (p < 0.01) and 23.3 +/- 19.1% (p < 0.001) by probucol treatment while LDL1-TG concentration was unchanged. Absolute amounts of plasma small, heavy LDL(LDL2)-TC, LDL2-TG, LDL2-PL and LDL2-apoB levels remained unchanged but percent increases of LDL2-TC and LDL2-apoB were statistically significant (p < 0.05). 2-16% gradient polyacrylamide gel electrophoresis demonstrated the diminution of LDL of large size by probucol treatment. Probucol markedly reduced plasma high density lipoprotein levels. The reductions of HDL2-TC, HDL2-TG, HDL2-PL and HDL2-apoAI concentrations were 36.2 +/- 25.4% (p < 0.001), 25.8 +/- 36.9% (p < 0.01), 34.4 +/- 23.8% (p < 0.001) and 35.6 +/- 28.4% (p < 0.001). Probucol significantly decreased plasma HDL3-TC, HDL3-PL and HDL3-apoAI amounts by 17.4 +/- 22.9% (p < 0.01), 18.3 +/- 20.8% (p < 0.01) and 19.8 +/- 27.9% (p < 0.01) without change of HDL3-TG level. The decrease of HDL2 level was more marked than that of HDL3 level. Probucol did not change LCAT activities. Probucol significantly stimulated CETP activities from 126.6 +/- 50.6 units to 172.8 +/- 40.2 units by 12 week treatment (p < 0.001). We concluded that probucol decreased plasma LDL1, HDL2 and HDL3 amounts and made them triglyceride-rich with the concomitant increase of CETP activities.</p>","PeriodicalId":75564,"journal":{"name":"Artery","volume":"20 1","pages":"1-18"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19431759","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}