Relationship between plasma plasminogen activator inhibitor-1 activity and VLDL triglyceride concentration, insulin levels and insulin sensitivity: studies in randomly selected normo- and hypertriglyceridaemic men

Asplund-Carlson, Anette; Hamsten, Anders; Wiman, Björn; Carlson, Lars A.

doi:10.1007/bf00400356

Cited by 123 publications

(76 citation statements)

References 47 publications

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“…Although the correlations classically found [43][44][45] between the markers of fibrinolysis or endothelial damage and triglycerides are observed in both subgroups of female patients, positive correlations are observed between PAI-1 activity or PAI-1 antigen and triglycerides as well as the 2 markers of remnant accumulation only in the hypertriglyceridemic subgroup of male patients. In vitro, it has been shown that VLDLs stimulate the production of PAI-1 by hepatic cells and endothelial cells.…”

Section: Bard Et Almentioning

confidence: 74%

Accumulation of Triglyceride-Rich Lipoprotein in Subjects With Abdominal Obesity

Bard

Munier

Juhan‐Vague

et al. 2001

ATVB

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Abstract-The present study represents a new insight into the Biguanides and the Prevention of the Risk of Obesity (BIGPRO) 1 study population at inclusion. This population, selected basically on the basis of a high waist-to-hip ratio (Ն0.95 for men and Ն0.80 for women), is supposed to represent a group of patients with insulin resistance. The present study was undergone to establish whether apolipoprotein C-III (apoC-III) and apolipoprotein E (apoE) associated with apo B (apoC-III LpB and apoE LpB, respectively), considered to be markers of remnant accumulation, play a role in the hypertriglyceridemia associated with insulin resistance and whether they are related to other biological abnormalities frequently observed in this syndrome. In this population, the concentration of the markers of remnant accumulation increases with triglyceride levels. Therefore, correlation studies were realized to assess the relative effect of insulin and the markers of remnant accumulation on triglyceride plasma level. As a first attempt, a simple correlation analysis revealed that insulin is positively related to the markers of remnant accumulation only in hypertriglyceridemic patients (triglycerides Ն1.7 mmol/L). To assess the independent contribution of these markers, insulin, and other parameters related to the plasma triglyceride concentration, a stepwise multiple regression analysis was run. Results revealed that insulin and the markers of remnant accumulation (specifically, apoE LpB) are independent contributors to the plasma triglyceride concentration. Markers of the endothelial damage, plasminogen activator inhibitor-1, tissue plasminogen activator, and von Willebrand factor, which are often increased in the case of insulin resistance, were tested for their correlation with the markers of remnant accumulation. Plasminogen activator inhibitor-1 is positively correlated with these markers only in hypertriglyceridemic male subjects. It is concluded that increased insulin levels found in insulin resistance syndrome are associated with an increased production of triglyceride-rich lipoproteins enriched in apoC-III and apoE. The accumulation of these remnants and/or their abnormal composition in apoC-III and apoE could be an explanation for the development of hypertriglyceridemia in this syndrome. nsulin resistance syndrome includes a constellation of clinical and biological anomalies, clustering in subjects with upper body fat distribution who often exhibit insulin resistance at the cell level. 1-4 Among these anomalies are hyperinsulinemia, glucose intolerance, elevated blood pressure, impaired fibrinolytic activity, and a dyslipidemic profile characterized by a high plasma triglyceride concentration and a low HDL cholesterol level. 5,6 Triglyceride-rich lipoproteins (TGRLs) represent a mixture of particles in which apoC-III and apoE are present in multiple copies. 7 During the lipolytic process, most apoCs and apoEs are transferred to HDL. 8 -11 In addition, apoC-III inhibits lipolysis, 12-14 and apoE plays a role in the clear...

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Section: Bard Et Almentioning

confidence: 74%

Accumulation of Triglyceride-Rich Lipoprotein in Subjects With Abdominal Obesity

Bard

Munier

Juhan‐Vague

et al. 2001

ATVB

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“…Smoking is associated with increased levels of procoagulative factors, e.g. fibrinogen [35] and reduced fibrinolytic capacity [36], while moderate alcohol consumption has been shown to influence the levels of fibrinolytic factors [37][38][39]. In fact haemostatic factors have been suggested to be on the eventual pathway to the protective effect of alcohol.…”

Section: Discussionmentioning

confidence: 99%

Alcohol and coronary heart disease: the roles of HDL‐cholesterol and smoking

Mänttäri

Tenkanen²,

Alikoski³

et al. 1997

Journal of Internal Medicine

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Abstract. Man$ tta$ ri M, Tenkanen L, Alikoski T, Manninen V (Department of Medicine, Helsinki University and Helsinki Heart Study, Helsinki, Finland). Alcohol and coronary heart disease : the roles of HDL-cholesterol and smoking. J. Intern Med 1997 ; 241 : 157-63. Objectives.To study the role of HDL-cholesterol (HDLc) in the causal pathway mediating the effect of alcohol on coronary heart disease (CHD). Design. Cox proportional hazard models were used to compare the relative CHD risks in various HDLcsmoking categories. Setting. A prospective, multicentre, placebocontrolled, double-blind CHD primary prevention trial with gemfibrozil in primary (occupational) health care units, the Helsinki Heart Study. Subjects. Dyslipidaemic middle-aged men with available alcohol consumption data (1924 of 2035) in the placebo arm of the 5-year study. Main outcome measures. Seventy-seven (of 84) cases of nonfatal myocardial infarction or cardiac death.

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“…20 We therefore hypothesized that the distribution of the 4G/5G genotype may differ between non-Hispanic whites, Hispanics, and blacks. Because core features of the insulin resistance syndrome, including serum lipids, measures of body weight, and insulin resistance, are major determinants of circulating PAI-1 levels, [21][22][23][24][25][26] and ethnic differences exist with respect to these features, [27][28][29][30][31][32][33][34] we also studied in the 3 ethnic groups the relation of the 4G/5G genotype to PAI-1 levels considering metabolic covariates, including serum lipids, body weight, and insulin resistance (S I ). The aim of the present study was to investigate in a large, tri-ethnic population comprising non-Hispanic whites, Hispanics, and blacks the frequency of the 4G/5G PAI-1 promoter genotype, the relation of the genotype to circulating PAI-1 levels, and the relative contribution of the genotype to PAI-1 levels, taking into account metabolic cofactors, including S I , as measured directly by a frequently sampled intravenous glucose tolerance test (FSIGTT).…”

mentioning

confidence: 99%

Promoter (4G/5G) Plasminogen Activator Inhibitor-1 Genotype and Plasminogen Activator Inhibitor-1 Levels in Blacks, Hispanics, and Non-Hispanic Whites

et al. 2003

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Background-The 4G/5G polymorphism of the plasminogen activator inhibitor-1 (PAI-1) gene has been related to cardiovascular disease. Methods and Results-Insulin resistance was measured with a frequently sampled intravenous glucose tolerance test in the Insulin Resistance Atherosclerosis Study (IRAS), and PAI-1 4G/5G promoter genotype was established by allelespecific polymerase chain reaction amplification of genomic DNA. There were 287 subjects with the 4G/4G genotype (18.4%), 691 heterozygote subjects (44.2%), and 586 carriers of the 5G/5G genotype (37.5%). The genotype distribution was different across the 3 ethnic groups (Pϭ0.001). PAI-1 levels were lower in blacks than in non-Hispanic whites and Hispanics and lower in non-Hispanic whites than in Hispanics (all Pϭ0.0001). Subjects homozygous for the 4G allele had the highest plasma PAI-1, heterozygote subjects were intermediate, and 5G homozygotes had the lowest levels of PAI-1. These patterns remained unaffected by adjustments for age, gender, clinical center, glucose tolerance status, body mass index, waist, triglycerides, and insulin resistance. Multiple linear regression analyses showed that the 4G/5G genotype explained very little of the variation in PAI-1 levels (0.63% in non-Hispanic whites, 0.99% in Hispanics, and 2.37% in blacks), and interaction analyses revealed no significant differences in the relation of circulating PAI-1 levels to the 4G/5G genotype by ethnicity (Pϭ0.4). Conclusions-We have shown ethnic differences in the PAI-1 4G/5G polymorphism along with corresponding differences in circulating PAI-1 levels. The association of the genotype with PAI-1 levels was seen consistently among all 3 ethnic groups and was unaffected by metabolic covariates, including insulin resistance. (Circulation. 2003;107:2422-2427.)

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Relationship between plasma plasminogen activator inhibitor-1 activity and VLDL triglyceride concentration, insulin levels and insulin sensitivity: studies in randomly selected normo- and hypertriglyceridaemic men

Cited by 123 publications

References 47 publications

Accumulation of Triglyceride-Rich Lipoprotein in Subjects With Abdominal Obesity

Accumulation of Triglyceride-Rich Lipoprotein in Subjects With Abdominal Obesity

Alcohol and coronary heart disease: the roles of HDL‐cholesterol and smoking

Promoter (4G/5G) Plasminogen Activator Inhibitor-1 Genotype and Plasminogen Activator Inhibitor-1 Levels in Blacks, Hispanics, and Non-Hispanic Whites

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