PAI-1 Produced Ex Vivo by Human Adipose Tissue Is Relevant to PAI-1 Blood Level

Morange, Pierre‐Emmanuel; Alessi, Marie‐Christine; Verdier, Monique; Casanova, Daniel; Magalon, G.; Juhan‐Vague, I.

doi:10.1161/01.atv.19.5.1361

Cited by 101 publications

(86 citation statements)

References 43 publications

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“…6,7,16 Yet, the observation of similar and minor PAI-1 mRNA expression in native human visceral and subcutaneous adipose tissue 7,17,18 is not consistent with such a mechanism. Moreover, we found strong indications that the observed PAI-1 release from adipose tissue explants on in vitro incubation relates to an incubation artifact and may not necessarily reflect the in vivo situation.…”

Section: Discussionmentioning

confidence: 91%

Human visceral adipose tissue and the plasminogen activator inhibitor type 1

Lindeman

Pijl

Toet³

et al. 2007

Int J Obes

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Objective: The objective of this study was to systematically evaluate the molecular basis of the association between visceral fat mass and plasma plasminogen activator inhibitor-1 (PAI-1) levels in man. Design: A comprehensive approach comprising observational, in vitro, and human intervention studies. Measurements and results:We confirmed an exclusive relationship between visceral fat and plasma PAI-1 levels (r ¼ 0.79, Po0.001) and corroborated preferential PAI-1 release from adipose tissue explants. Yet, messenger RNA analysis and in vivo measurement of PAI-1 release from visceral fat (AV-differences over the omentum) not only excluded visceral adipose tissue as a relevant source of circulating PAI-1, but also excluded visceral fat as a significant source of proinflammatory mediators such as tumor necrosis factor-a, IL-1 or transforming growth factor-b that could induce PAI-1 expression in tissues other than visceral fat. Short-term interventions with acipimox and growth hormone (GH) as well as statistical evaluation excluded free fatty acids and GH as metabolic links. Further analysis of the metabolic data in a stepwise regression model indicated that plasma PAI-1 levels and visceral fat rather are co-correlates that both relate to impaired lipid handling. Conclusion: Our PAI-1 studies show that visceral fat mass and plasma PAI-1 levels are co-correlated rather than causatively related, with lipid load as common denominator.

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Section: Discussionmentioning

confidence: 91%

Human visceral adipose tissue and the plasminogen activator inhibitor type 1

Lindeman

Pijl

Toet³

et al. 2007

Int J Obes

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“…10,12,14 These findings, together with our present results, suggest a link between overweight/obesity and ischemic stroke independent of established risk factors. Some investigators have proposed that the increase in prothrombotic factors [27][28][29] and inflammatory markers, [30][31][32][33] and the enhancement of insulin resistance and metabolic syndrome 34 observed among overweight and obese individuals may have a role in their increased risk of ischemic stroke. Our stratified analysis showed an extremely increased risk of ischemic stroke in men who have both obesity and diabetes or smoking habits.…”

Section: Discussionmentioning

confidence: 99%

Body mass index and stroke incidence in a Japanese community: the Hisayama study

et al. 2010

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Although obesity is one of the major risk factors for coronary heart disease, its role in the development of stroke remains controversial. A total of 2421 residents, aged 40-79 years of a Japanese community were followed up prospectively for 12 years. The subjects were divided into four groups according to body mass index (BMI) levels (o21.0, 21.0-22.9, 23.0-24.9 and X25.0 kg m À2 ). During the follow-up, 107 ischemic and 51 hemorrhagic strokes occurred. The age-adjusted incidence of ischemic stroke for men significantly increased with increasing BMI levels (P for trend¼0.005). This association remained substantially unchanged even after adjustment for other risk factors: namely, systolic blood pressure, electrocardiogram abnormalities, diabetes, total cholesterol, high-density lipoprotein-cholesterol, triglycerides, smoking habits, alcohol intake and regular exercise (P for trendo0.001). Compared with that of the BMI levels of o21.0 kg m À2 , the multivariate-adjusted risk of ischemic stroke was significant even in the BMI levels of 23.0-24.9 kg m À2 (multivariate-adjusted hazard ratio (HR)¼3.12; 95% confidence interval (CI), 1.24-7.87; P¼0.02) as well as in the BMI levels of X25 kg m À2 (multivariate-adjusted HR¼5.59; 95% CI, 2.09-14.91; Po0.001). In stratified analyses, the risk of ischemic stroke for men synergistically increased in subjects having both obesity and diabetes or a smoking habit. We found no significant associations between BMI levels and ischemic stroke in women and between BMI levels and hemorrhagic stroke in either sex. In conclusion, our findings suggest that overweight and obesity are independent risk factors for ischemic stroke in Japanese men.

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“…Our results clearly showed that PAI-1 expression is not uniformly distributed within human subcutaneous adipose tissue, suggesting that regulation of PAI-1 expression must be different in various body fat regions. It has been previously shown that visceral tissue explants produce more PAI-1 than explants from abdominal subcutaneous tissue [11,13,28]. However, the strong correlations observed between PAI-1 production from both abdominal fat depots (visceral and subcutaneous) and markers of insulin resistance, have led investigators to conclude that, in both tissues, PAI-1 production is controlled by a similar pathway [13].…”

Section: Discussionmentioning

confidence: 99%

Subcutaneous abdominal, but not femoral fat expression of plasminogen activator inhibitor-1 (PAI-1) is related to plasma PAI-1 levels and insulin resistance and decreases after weight loss

et al. 2001

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Plasminogen activator inhibitor-1 (PAI-1) is the main inhibitor of tissue-type plasminogen activator and has an important role in regulating the fibrinolytic system and thrombus formation. Higher plasma PAI-1 concentrations impair fibrinolysis, which could account for its predictability for cardiovascular events [1,2]. Obesity, an independent risk factor for cardiovascular diseases is associated with increased plasma PAI-1 values [3,4].The mechanisms involved in increased PAI-1 production in obesity have not been fully explained. The insulin-resistance syndrome, a cluster of metabolic abnormalities, accompanying visceral types of obesity could be an important regulator of PAI-1 expression. Indeed, all the variables related to the insulin resistance syndrome (insulinaemia, BMI, waistto-hip ratio (WHR), serum triglyceride and HDL cholesterol concentration) are strongly related to Diabetologia (2001 Subcutaneous abdominal, but not femoral fat expression of plasminogen activator inhibitor-1 (PAI-1) is related to plasma PAI-1 levels and insulin resistance and decreases after weight loss Abstract Aims/hypothesis. Abdominal fat produces plasminogen activator inhibitor-1 (PAI-1) and could contribute to increased plasma PAI-1 values in human obesity associated with insulin resistance. Femoral fat, which is not associated with insulin resistance, is thought to be metabolically different from the abdominal fat. This study aimed to assess PAI-1 expression in these two fat territories in obese and lean subjects and to determine if concomitant changes of plasma and adipose tissue PAI-1 values occur after weight reduction.Methods. In 24 obese and 16 lean subjects, PAI-1 expression in abdominal and femoral subcutaneous fat, plasma PAI-1, insulin, triglyceride concentrations and insulin resistance were determined at the start of the study and in obese subjects after a 3-month weight reduction programme as well.Results. PAI-1 mRNA content in the abdominal subcutaneous fat was higher in obese than in lean subjects and positively correlated with plasma PAI-1 values (p < 0.01) and markers of insulin resistance (p < 0.05). In 18 obese subjects, re-examined after successful dieting, PAI-1 mRNA content decreased in the abdominal subcutaneous fat along with plasma PAI-1. However, the absolute changes of these two variables were not associated. In contrast, PAI-1 mRNA content in the femoral subcutaneous fat did not differ between lean and obese subjects, was not associated with plasma PAI-1 values or with markers of insulin resistance, and did not change after weight loss. Conclusion/interpretation. Only the abdominal, but not the femoral subcutaneous fat PAI-1 expression is a potential contributor to increases in plasma PAI-1 in obesity. Both plasma and abdominal subcutaneous fat PAI-1 values decreased significantly after weight reduction, although their absolute changes were not associated. [Diabetologia (2001

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PAI-1 Produced Ex Vivo by Human Adipose Tissue Is Relevant to PAI-1 Blood Level

Cited by 101 publications

References 43 publications

Human visceral adipose tissue and the plasminogen activator inhibitor type 1

Human visceral adipose tissue and the plasminogen activator inhibitor type 1

Body mass index and stroke incidence in a Japanese community: the Hisayama study

Subcutaneous abdominal, but not femoral fat expression of plasminogen activator inhibitor-1 (PAI-1) is related to plasma PAI-1 levels and insulin resistance and decreases after weight loss

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