Arteriosclerosis (Dallas, Tex.)最新文献

{"title":"Antisera and monoclonal antibodies specific for epitopes generated during oxidative modification of low density lipoprotein.","authors":"W Palinski,&nbsp;S Ylä-Herttuala,&nbsp;M E Rosenfeld,&nbsp;S W Butler,&nbsp;S A Socher,&nbsp;S Parthasarathy,&nbsp;L K Curtiss,&nbsp;J L Witztum","doi":"10.1161/01.atv.10.3.325","DOIUrl":"https://doi.org/10.1161/01.atv.10.3.325","url":null,"abstract":"<p><p>Increasing evidence indicates that low density lipoprotein (LDL) has to be modified to induce foam cell formation. One such modification, oxidation of LDL, generates a number of highly reactive short chain-length aldehydic fragments of oxidized fatty acids capable of conjugating with lysine residues of apoprotein B. By immunizing animals with homologous malondialdehyde-modified LDL (MDA-LDL), 4-hydroxynonenal-LDL (4-HNE-LDL), and Cu+(+)-oxidized LDL, we developed polyvalent and monoclonal antibodies against three epitopes found in oxidatively modified LDL. The present article characterizes an antiserum and monoclonal antibody (MAL-2 and MDA2, respectively) specific for MDA-lysine, and an antiserum and monoclonal antibody (HNE-6 and NA59, respectively) specific for 4-HNE-lysine. In addition, a monoclonal antibody (OLF4-3C10) was developed against an as yet undefined epitope generated during Cu++ oxidation of LDL. With these antibodies, we demonstrated that MDA-lysine and 4-HNE-lysine adducts develop on apo-lipoprotein B during copper-induced oxidation of LDL in vitro. The application of these antibodies for immunocytochemical demonstration of oxidized lipoproteins in atherosclerotic lesions of progressive severity is described in the companion article. These antibodies should prove useful in studying the role of oxidatively modified lipoproteins as well as other oxidatively modified proteins in atherogenesis.</p>","PeriodicalId":77492,"journal":{"name":"Arteriosclerosis (Dallas, Tex.)","volume":"10 3","pages":"325-35"},"PeriodicalIF":0.0,"publicationDate":"1990-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/01.atv.10.3.325","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12857642","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":"Postprandial lipemia and lipoprotein lipase in the rabbit are modified by olive and coconut oil.","authors":"M Van Heek,&nbsp;D B Zilversmit","doi":"10.1161/01.atv.10.3.421","DOIUrl":"https://doi.org/10.1161/01.atv.10.3.421","url":null,"abstract":"<p><p>Feeding a 14% coconut oil/0.5% cholesterol (CNO/chol) diet to rabbits resulted in plasma triglycerides that were, on average, 15 times higher than basal levels. Plasma triglycerides in rabbits fed a 14% olive oil/0.5% cholesterol (OO/chol) diet were significantly below baseline levels. Differences in postprandial triglyceride response and postheparin plasma lipoprotein lipase activity (LPL) in various feeding conditions were studied to determine the mechanism of the hypertriglyceridemia. Postprandial triglyceride responses after the first high fat/cholesterol meal were more prolonged in CNO/chol rabbits than in OO/chol rabbits; postprandial triglyceride responses after chronic CNO/chol feeding were significantly greater compared to OO/chol rabbits. When long-term CNO/chol rabbits were given one OO/chol or corn oil/chol meal, postprandial triglyceride peaks were greatly diminished, suggesting that these unsaturated fat meals may alter triglyceride clearance capacity. LPL activity was 400% higher than basal levels in chronically fed OO/chol rabbits but changed very little in chronically fed CNO/chol rabbits. Twenty-four hours after a single OO/chol meal was fed to chow-fed rabbits, LPL doubled; one CNO/chol meal was associated with only a 40% increase. Feeding a single OO/chol or corn oil/chol meal to chronically fed CNO/chol rabbits resulted in a 30% to 50% increase in LPL by 24 hours. Thus, the hypertriglyceridemia in CNO/chol rabbits may result in part from a decreased clearance capacity due to a lack of increase in LPL activity, while increased LPL may be partially responsible for the hypotriglyceridemia observed in OO/chol feeding. Aortic cholesterol was substantially higher in CNO/chol rabbits. Triglyceride was approximately eight times greater in livers from CNO/chol-fed rabbits than in those fed OO/chol, but liver cholesterol was only about one-third as much as that in OO/chol rabbits.</p>","PeriodicalId":77492,"journal":{"name":"Arteriosclerosis (Dallas, Tex.)","volume":"10 3","pages":"421-9"},"PeriodicalIF":0.0,"publicationDate":"1990-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/01.atv.10.3.421","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13494076","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":"Persistent abnormalities in lipoprotein composition in noninsulin-dependent diabetes after intensive insulin therapy.","authors":"J D Bagdade,&nbsp;W E Buchanan,&nbsp;T Kuusi,&nbsp;M R Taskinen","doi":"10.1161/01.atv.10.2.232","DOIUrl":"https://doi.org/10.1161/01.atv.10.2.232","url":null,"abstract":"<p><p>To determine whether rigorous insulin therapy, which normalized the routinely measured plasma lipids, also reversed qualitative abnormalities in the composition of lipoproteins in noninsulin-dependent diabetes mellitus (NIDDM), we studied 18 NIDDM patients (eight men and 10 women) before and 2 months after intensive insulin therapy. Glycosylated hemoglobin levels (11.7% vs. 8.7%), plasma triglyceride (TG) (250 +/- 91 vs. 164 +/- 56 mg/dl, p less than 0.001), and cholesterol (214 +/- 43 vs. 198 +/- 31 mg/dl, p less than 0.025) all fell, and both HDL2 cholesterol and HDL3 cholesterol increased (59.1% and 10.9%, respectively, p less than 0.001). However, abnormalities in two indices of lipoprotein surface constituents, which were present before insulin therapy, remained so thereafter. The first of these, the new cardiovascular risk factor, the plasma free cholesterol/lecithin ratio, which was increased before treatment, fell only slightly after therapy (pre-therapy 1.02 +/- 0.29 vs. post-therapy 0.90 +/- 0.17, p less than 0.4; reference group, 0.83 +/- 0.14), and remained elevated in very low density lipoprotein (VLDL) and low density lipoprotein (LDL). Secondly, the sphingomyelin/lecithin ratio, an index of the surface rigidity of lipoproteins, was abnormal before treatment in VLDL, HDL2, and HDL3, and this alteration persisted after insulin therapy in HDL3 (p less than 0.001). Lipoprotein core lipid abnormalities were also present before treatment: the TG/cholesteryl ester ratio was reduced in VLDL and increased in LDL, HDL2, and HDL3. Rigorous insulin therapy improved, but failed to fully correct, this disturbance.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":77492,"journal":{"name":"Arteriosclerosis (Dallas, Tex.)","volume":"10 2","pages":"232-9"},"PeriodicalIF":0.0,"publicationDate":"1990-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/01.atv.10.2.232","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13333811","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":"Expression of elastase activity by human monocyte-macrophages is modulated by cellular cholesterol content, inflammatory mediators, and phorbol myristate acetate.","authors":"M Rouis,&nbsp;F Nigon,&nbsp;C Lafuma,&nbsp;W Hornebeck,&nbsp;M J Chapman","doi":"10.1161/01.atv.10.2.246","DOIUrl":"https://doi.org/10.1161/01.atv.10.2.246","url":null,"abstract":"<p><p>We investigated the effects of a number of stimulatory agents on the production of both cell-associated and extracellular elastase-type enzymes on human monocyte-macrophages in vitro and of the modulation of such effects by modification of cellular cholesterol content. The stimulatory agents included phorbol myristate acetate (PMA) and the inflammatory mediators, lipopolysaccharide (LPS), opsonized zymosan (OZ), and platelet activating factor (PAF). Using the synthetic substrate, N-succinyl-trialanyl-paranitroanilide (SANA), we detected cell-associated elastase-like activity in monocyte-derived macrophages. Such activity increased markedly with cell maturation over the period from 5 to 15 days of adherence culture. While PAF (10 micrograms/ml) and LPS (10 micrograms/ml) were without effect on cell-associated elastase-like activity in macrophages, PMA (100 ng/ml) and OZ (1 mg/ml) markedly stimulated such activity in cells cultured for 15 days. Furthermore, a fivefold increase in the cell-associated elastase-like activity of macrophages occurred upon cholesterol loading of the cells with acetylated low density lipoprotein (AcLDL). By contrast, this activity was markedly diminished upon depletion of cellular cholesterol content after incubation with high density lipoprotein (HDL3). Latent elastinolytic activity in the culture medium was detected by use of a radioactive substrate, insoluble 3H-elastin, after initial tryptic treatment of the medium. Such latent elastase activity was secreted only by activated macrophages; the relative potency of stimulation was: PMA greater than LPS = PAF greater than OZ. Increase in cellular cholesterol content alone markedly enhanced the secretion of elastase (from undetectable levels to 28 ng of 3H-elastin degraded/hr/micrograms DNA). In all cases, both the cell-associated and secreted latent elastinolytic activities were due to metalloproteases, in view of their 90% inhibition by 2 mM EDTA. Cholesterol-loaded macrophages, which displayed an approximately 40-fold increase in total cholesterol content as compared to control cells, remained sensitive to the action of activators of OZ and PMA, while LPS and PAF exerted only weak effects. Our data indicate that cellular cholesterol content and inflammatory mediators are effective stimulants of the production and secretion of elastase-type enzymes by human monocyte-macrophages. Among these factors, cellular cholesterol content, OZ, PAF, and LPS may represent factors of relevance to the inflammatory role of the macrophage in atherogenesis and more specifically to the alteration of elastin structure in the extracellular matrix of the vessel wall.</p>","PeriodicalId":77492,"journal":{"name":"Arteriosclerosis (Dallas, Tex.)","volume":"10 2","pages":"246-55"},"PeriodicalIF":0.0,"publicationDate":"1990-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/01.atv.10.2.246","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13466583","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":"Atherosclerosis susceptibility differences among progenitors of recombinant inbred strains of mice.","authors":"B Paigen,&nbsp;B Y Ishida,&nbsp;J Verstuyft,&nbsp;R B Winters,&nbsp;D Albee","doi":"10.1161/01.atv.10.2.316","DOIUrl":"https://doi.org/10.1161/01.atv.10.2.316","url":null,"abstract":"<p><p>Female mice of 16 inbred mouse strains were fed an atherogenic diet for 14 weeks and were then evaluated for atherosclerotic lesions in the aorta. Strains C57BL/6, C57BR/cd, C57L, and SM were very susceptible to atherosclerosis, with lesion area/aortic cross-sections in the range of 4500 to 8000 microns 2. Strains C58 and SWR were intermediate in susceptibility, with lesion area/sections in the range of 1670 to 1690 microns 2. Strains 129, AKR, DBA/2, and BALB/c had only small lesions in the range of 20 to 350 microns 2/section; strains C3H, NZB, CBA, HRS, SJL, and A had no lesions after 14 weeks. Lesion formation in five strains was compared at several time points. Strain C57BL/6 mice developed lesions by 7 weeks, and these continued to grow until all mice had large atheromatous plaques in the aorta and coronary arteries. Strains AKR and DBA/2 also had fatty streak lesions as early as 7 or 8 weeks, but these lesions had not progressed in size by 14 weeks. Strains BALB/c and C3H, which were both resistant to lesion formation at 14 weeks, diverged from each other as time progressed. By 1 year, BALB/c mice had large lesions, but C3H mice had none. Most of the inbred strains chosen for evaluation are the progenitors of recombinant inbred sets of strains, a genetic tool that greatly facilitates the analysis of strain differences. This survey indicates seven additional recombinant inbred sets of strains whose progenitors differ in atherosclerosis susceptibility: BXD, AKXL, SWXJ, NX8, 129XB, NXSM, and B6NXAKRN. An analysis of these recombinant inbred strains may reveal additional mouse genes affecting atherosclerosis susceptibility.</p>","PeriodicalId":77492,"journal":{"name":"Arteriosclerosis (Dallas, Tex.)","volume":"10 2","pages":"316-23"},"PeriodicalIF":0.0,"publicationDate":"1990-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/01.atv.10.2.316","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13467149","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":"Atherogenesis during low level hypercholesterolemia in the nonhuman primate. I. Fatty streak formation.","authors":"J Masuda,&nbsp;R Ross","doi":"10.1161/01.atv.10.2.164","DOIUrl":"https://doi.org/10.1161/01.atv.10.2.164","url":null,"abstract":"<p><p>Although a large body of data is available concerning atherogenesis in animals maintained at high levels of hypercholesterolemia, little data are available for animals maintained at lower levels of hypercholesterolemia for longer periods of time, closer to those observed in humans. The chronologic sequence of cellular events and interactions that occur during the formation of the lesions of atherosclerosis was investigated during relatively low level hypercholesterolemia (200 to 400 mg/dl) in a series of nonhuman primates (Macaca nemestrina). The arterial tree of each animal was examined by light microscopy and scanning and transmission electron microscopy. Immunohistochemical staining with monoclonal antibodies specific for smooth muscle cells, monocyte-macrophages, and T-lymphocytes was performed to analyze the cellular composition of the lesions. After 6 months of low level hypercholesterolemia, the surface of the aorta contained large numbers of adherent leukocytes, many of which were in the process of entering the artery. This resulted in irregularly shaped nodular elevations, or fatty streaks, preferentially located at branch sites and bifurcations. The fatty streaks consisted of intimal accumulations of numerous lipid-laden macrophages together with relatively small numbers of T-lymphocytes. With lesion progression, the thickness of the fatty streaks increased, and their surfaces became irregular and frequently showed disruptions of covering endothelial cells resulting in exposure of subendothelial macrophages. Platelet microthrombi were observed over some of the exposed macrophages at some branches or bifurcations in every animal studied. These observations made during the early phases of atherosclerosis lesion formation are virtually identical to those described in our previous reports in high level hypercholesterolemic nonhuman primates (600 to 1000 mg/dl) with the exception that the changes occurred more slowly in the lower levels of hypercholesterolemia.</p>","PeriodicalId":77492,"journal":{"name":"Arteriosclerosis (Dallas, Tex.)","volume":"10 2","pages":"164-77"},"PeriodicalIF":0.0,"publicationDate":"1990-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/01.atv.10.2.164","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13333216","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":"Macromolecular transport across arterial and venous endothelium in rats. Studies with Evans blue-albumin and horseradish peroxidase.","authors":"P T Chuang,&nbsp;H J Cheng,&nbsp;S J Lin,&nbsp;K M Jan,&nbsp;M M Lee,&nbsp;S Chien","doi":"10.1161/01.atv.10.2.188","DOIUrl":"https://doi.org/10.1161/01.atv.10.2.188","url":null,"abstract":"<p><p>Atherosclerotic lesions are characterized by lipid infiltration in regions with high rates of endothelial cell turnover. The present investigation was designed to elucidate the route of macromolecular transport across vascular endothelium. The aorta and vena cava of male Sprague-Dawley rats were perfusion-fixed after the intravenous injection of Evans-blue albumin (EBA) or horseradish peroxidase (HRP). Fluorescence microscopic examination of en face preparation of the aorta stained with hematoxylin allowed the identification of endothelial cells that underwent mitosis, together with the localization and quantification of fluorescent spots for EBA leakage. The HRP specimens were subjected to histochemical treatment, and HRP leakage was seen as brown spots under the light microscope. Silver nitrate stain was added in both EBA and HRP studies to outline cell boundaries and to visualize stigmata, stomata, and dead cells. In the aorta, almost every dividing cell showed junctional leakage to albumin and HRP, with clustering of leaky spots around the branch orifices. Time-dependent studies showed gradual increases in the diameter and number of these heterogeneously sized leaky spots, which finally fused to sizes corresponding to the \"blue areas\" for EBA or \"brown areas\" for HRP. Compared with arteries, veins had fewer mitotic cells, but more dead cells and diffuse dye-staining areas, indicating a more rapid transport of macromolecules. The leaky spots in the artery were associated mainly with mitotic cells, dead cells, and stigmata, whereas those in the vein occurred primarily at regions with dead cells. These results suggest that the preferential association of the enhanced transport of macromolecules with mitosis in the arterial as compared to venous endothelium and the differential behavior in transmural transport between arteries and veins may form the basis for the predilection of atherosclerosis in arteries.</p>","PeriodicalId":77492,"journal":{"name":"Arteriosclerosis (Dallas, Tex.)","volume":"10 2","pages":"188-97"},"PeriodicalIF":0.0,"publicationDate":"1990-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/01.atv.10.2.188","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13333807","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":"Apolipoprotein E4 homozygosity predisposes to serum cholesterol elevation during high fat diet.","authors":"M J Tikkanen,&nbsp;J K Huttunen,&nbsp;C Ehnholm,&nbsp;P Pietinen","doi":"10.1161/01.atv.10.2.285","DOIUrl":"https://doi.org/10.1161/01.atv.10.2.285","url":null,"abstract":"<p><p>The hypothesis that apolipoprotein E (apo E)-isoform-related differences in plasma and LDL cholesterol concentrations are due to differential responses to dietary lipids was explored in 110 North Karelian subjects who had previously participated in dietary intervention studies. This was accomplished by collecting fresh blood samples for apo E phenotyping and by re-analysis of the original plasma lipid data according to apo E phenotypes. During high fat, high cholesterol baseline (p = 0.003) and switchback diets (p = 0.002), plasma cholesterol correlated inversely with the sum of subscript numbers (e.g., apo E3/4 = 7). Thus, subjects with the apo E4/4 phenotype had the highest (7.63 +/- 1.32 mmol/l), and subjects with the apo E3/2 phenotype had the lowest baseline levels of plasma cholesterol (5.85 +/- 1.48 mmol/l). This association became weaker during a low fat, low cholesterol diet intervention (p = 0.069). Greater reductions in plasma cholesterol occurred in subjects homozygous for the apo epsilon 4 allele (-1.84 mmol/l) as compared to subjects with other genotypes (-1.13 mmol/l) (p = 0.0097). Moreover, these subjects responded to the switchback diet by greater increases in plasma cholesterol (1.52 mmol/l) than others (0.92 mmol/l, p = 0.0141). The results suggest that the effect of apo epsilon genotype on plasma cholesterol is modulated by dietary fat and cholesterol intake.</p>","PeriodicalId":77492,"journal":{"name":"Arteriosclerosis (Dallas, Tex.)","volume":"10 2","pages":"285-8"},"PeriodicalIF":0.0,"publicationDate":"1990-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/01.atv.10.2.285","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13466587","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":"Suppression of aortic atherosclerosis in cholesterol-fed rabbits by purified rabbit interferon.","authors":"A C Wilson,&nbsp;R G Schaub,&nbsp;R C Goldstein,&nbsp;P T Kuo","doi":"10.1161/01.atv.10.2.208","DOIUrl":"https://doi.org/10.1161/01.atv.10.2.208","url":null,"abstract":"<p><p>The effectiveness of rabbit interferon in suppressing atherosclerosis was evaluated in rabbits fed a diet containing 1% cholesterol. Ten male New Zealand White rabbits received intramuscular injections of 1 million units of interferon twice a week, while a control group of 10 rabbits received injections of buffer. Both groups had average serum cholesterol levels of over 2000 mg/dl during the 8-week experimental period. Interferon treatment resulted in no significant hypolipidemic effect or changes in lipoprotein composition. Atherosclerotic lesions in aortas were quantified both macroscopically and microscopically. Interferon treatment decreased the grossly visible lesion area significantly from 25 +/- 4% to 8 +/- 1% (mean +/- SEM, p less than 0.005) compared to the untreated group. Microscopic analysis of serial cross-sections of aortic segments revealed significant (p less than 0.01) reductions in both lesion size and frequency in the interferon-treated group. Electron microscopy also showed that interferon treatment reduced the pathological effects of cholesterol feeding. Tissue analysis showed that total aortic cholesterol was reduced by 28% by interferon treatment, while the aortic phospholipid concentration was increased by 25%. The possibility exists that the interferon preparation used contained other biological response modifiers and that the observed effects may be totally unrelated with interferon. These results suggest that the mechanism of atherosclerosis suppression in these cholesterol-fed rabbits is not related to the lowering of serum cholesterol but may be associated with inhibition of lesion initiation.</p>","PeriodicalId":77492,"journal":{"name":"Arteriosclerosis (Dallas, Tex.)","volume":"10 2","pages":"208-14"},"PeriodicalIF":0.0,"publicationDate":"1990-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/01.atv.10.2.208","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12854876","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":"Insulin resistance is associated with lipid and lipoprotein abnormalities in subjects with varying degrees of glucose tolerance.","authors":"M Laakso,&nbsp;H Sarlund,&nbsp;L Mykkänen","doi":"10.1161/01.atv.10.2.223","DOIUrl":"https://doi.org/10.1161/01.atv.10.2.223","url":null,"abstract":"<p><p>We tested the hypothesis that insulin resistance, rather than high insulin level, is associated with lipid and lipoprotein changes favoring atherosclerosis independently of the glucose tolerance status. To this aim, 50 subjects with normal glucose tolerance, 28 subjects with impaired glucose tolerance, and 54 subjects with noninsulin-dependent diabetes (NIDDM) were studied. Subjects with low glucose disposal rate (GDR) or a high degree of insulin resistance as measured by the euglycemic hyperinsulinemic clamp technique had lower high density lipoprotein (HDL) cholesterol and higher total and very low density lipoprotein (VLDL) triglycerides than did subjects with high GDR (highest GDR tertile). These associations were independent of fasting insulin level and other confounding factors. In stepwise multiple linear regression analysis, GDR was the most important single variable associated with HDL cholesterol and VLDL triglyceride level independently of age, obesity, distribution of obesity (waist/hip ratio), 2-hour glucose level, and free fatty acid concentration. We conclude: 1) insulin resistance measured by the euglycemic clamp technique is associated with adverse lipid and lipoprotein changes favoring atherosclerosis not only in nondiabetic subjects (as shown in previous studies) but also in impaired glucose tolerance and NIDDM subjects; 2) the association of high insulin level with adverse lipid and lipoprotein changes indirectly reflects the association of insulin resistance with lipid and lipoprotein levels; and 3) HDL cholesterol and VLDL triglycerides are independently associated with insulin-mediated glucose uptake, which may indicate that these lipoproteins have separate sites of interaction with insulin action.</p>","PeriodicalId":77492,"journal":{"name":"Arteriosclerosis (Dallas, Tex.)","volume":"10 2","pages":"223-31"},"PeriodicalIF":0.0,"publicationDate":"1990-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/01.atv.10.2.223","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13333810","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}