VLDL activation of plasminogen activator inhibitor-1 (PAI-1) expression: Involvement of the VLDL receptor

Nilsson, Lars‐Erik; Gåfvels, Mats; Musakka, Leena; Ensler, K.; Strickland, Dudley K.; Angelin, Bo; Hamsten, Anders; Eriksson, Per

doi:10.1016/s0021-9150(99)80437-7

Cited by 15 publications

(18 citation statements)

References 29 publications

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“…In addition, an independent predictive role of serum TG levels was also established, a finding in accordance with the ability of TG-very rich LDLs to induce the secretion of PAI-1 in cultured endothelial cells [33] and to up-regulate PAI-1 gene expression [34]. The overall ability of the above mentioned factors to affect PAI-1 production and plasma levels was evidenced by our observation that a multivariate model including these three factors and adjusted for age explained 23% of the total variability of PAI-1 level, a result unaffected by further adjustment for concomitant pharmacological treatments.…”

Section: Discussionsupporting

confidence: 69%

Relationships of PAI-1 levels to central obesity and liver steatosis in a sample of adult male population in southern Italy

Barbato¹,

Iacone²,

Tarantino³

et al. 2009

Intern Emerg Med

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To analyse the relationship of PAI-1 plasma levels to echographically determined liver steatosis and cardiometabolic risk factors in a randomly selected sample of 254 adult male participants of the Olivetti Heart Study. Accounting for age and ongoing pharmacological treatment, PAI-1 levels were directly (P < 0.005) associated with body mass index (BMI), waist circumference (WC), serum triglyceride (TG), total cholesterol, insulin, homeostasis model assessment index, gamma-glutamyl transpeptidase and peritoneal fat. At multiple linear regression (MLR) analysis, measures of adiposity and TG exerted significant and quantitatively similar effects on PAI-1 levels. A progressive rise in PAI-1 level was detected with increasing degree of steatosis. A stepwise MLR model was used to evaluate the relative power of cardiometabolic risk factors and liver steatosis on PAI-1 levels. Adjusting for alcohol intake, BMI, WC and peritoneal fat were alternatively included in the model with other variables found to be significantly associated with plasma PAI-1 level. Liver steatosis, serum TG and various indexes of adiposity each had a significant independent impact on PAI-1 plasma level and explained overall 23% of its variability. Abdominal fat, liver steatosis and serum TG levels were significant and independent determinants of PAI-1 plasma level in an unselected sample of adult male population upon adjustment for age and therapy.

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Section: Discussionsupporting

confidence: 69%

Relationships of PAI-1 levels to central obesity and liver steatosis in a sample of adult male population in southern Italy

Barbato¹,

Iacone²,

Tarantino³

et al. 2009

Intern Emerg Med

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“…Although altering the binding capabilities of receptors using antibodies is not a new approach (see: Argraves et al, 1997;Hummel et al, 2003;Nilsson et al, 1999;Oganesian et al, 2008;Perman et al, 2011), this study is, to the best of our knowledge, the first to employ this approach to block these particular receptors in any fish species. Addition of the vtgr antiserum appeared to have no effect on oocyte or oil droplet surface area, at least not during previtellogenic oocyte growth.…”

Section: Discussionmentioning

confidence: 98%

How do eggs get fat? Insights into ovarian fatty acid accumulation in the shortfinned eel, Anguilla australis

Damsteegt

Mizuta

Hiramatsu

et al. 2015

General and Comparative Endocrinology

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“…[42][43][44] Recently, it was shown that the PAI-1 promoter contains sequences able to bind free fatty acids or VLDL response elements. 45,46 Thus, free fatty acids might induce PAI-1 gene expression in the liver directly.…”

Section: Discussionmentioning

confidence: 99%

Plasma PAI-1 Levels Are More Strongly Related to Liver Steatosis Than to Adipose Tissue Accumulation

Alessi

Bastelica

Mavri

et al. 2003

ATVB

170

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Objective-Because obesity and insulin resistance (IR) are strongly associated with liver steatosis (LS), we investigated the relation between the degree of LS and plasminogen activator inhibitor-1 (PAI-1) in ob/ob mice, in C57/BL6 mice with alcoholic LS, and in severely obese humans. Methods and Results-In both mouse models, plasma PAI-1 levels were associated with PAI-1 expression in the liver and with the degree of LS. Liver PAI-1 antigen was associated with the tumor necrosis factor receptor-II (TNFRII) antigen, whereas association with TNF antigen content was found in ob/ob mice only. No significant correlation between plasma PAI-1 and PAI-1 expression in adipose tissue of ob/ob mice was observed. Furthermore, the relation between plasma PAI-1 levels and body weight was positive in ob/ob mice but negative in C57/BL6 mice (both PϽ0.001). In humans, PAI-1 levels were correlated with the degree of LS, and 26% of plasma PAI-1 activity was independently explained by LS and serum insulin levels. Conclusions-Plasma PAI-1 levels are more closely related to fat accumulation and PAI-1 expression in the liver than in adipose tissue. In steatotic liver, PAI-1 antigen content is associated with those of TNF and TNFRII. Therefore, we suggest that TNF pathway dysregulation in LS could be involved in increased plasma PAI-1 in obesity with IR. Key Words: liver steatosis Ⅲ PAI-1 Ⅲ adipose tissue Ⅲ insulin resistance P lasminogen activator inhibitor type 1 (PAI-1) is the main inhibitor of fibrinolysis. PAI-1 modulates the development of atherosclerosis in mice, 1,2 and an elevated plasma PAI-1 concentration is predictive for myocardial infarction in humans. 3,4 Interestingly, the predictive value of circulating PAI-1 levels is highly dependent on the insulin resistance syndrome. 4,5 Despite several efforts in the last few years, the mechanism of increased plasma PAI-1 concentration in insulin resistance associated with android obesity is not completely understood. PAI-1 is expressed in murine as well as in human adipose tissue, 6 -9 and its expression in adipose tissue is correlated positively with body mass index (BMI). 9 -11 Human visceral adipose tissue expresses more PAI-1 than does subcutaneous abdominal adipose tissue. 7,12 Furthermore, PAI-1 expression in only abdominal, but not in femoral subcutaneous adipose tissue, is associated with the features of insulin resistance. 11 Therefore, it has been postulated that in the insulin resistance syndrome with central obesity, abdominal adipose tissue is an important source of plasma PAI-1. Of note, an increase in plasma PAI-1 is also observed in lipodystrophy associated with antiretroviral treatment in HIV patients. These patients typically have prominent, peripheral fat wasting and maintained or decreased visceral fat depots and are insulin resistant. Interestingly, the difference in plasma PAI-1 levels between HIV patients and healthy controls was independent of HIV infection status and was not affected after adjustment for visceral fat estimation but was rather explained by...

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VLDL activation of plasminogen activator inhibitor-1 (PAI-1) expression: Involvement of the VLDL receptor

Cited by 15 publications

References 29 publications

Relationships of PAI-1 levels to central obesity and liver steatosis in a sample of adult male population in southern Italy

Relationships of PAI-1 levels to central obesity and liver steatosis in a sample of adult male population in southern Italy

How do eggs get fat? Insights into ovarian fatty acid accumulation in the shortfinned eel, Anguilla australis

Plasma PAI-1 Levels Are More Strongly Related to Liver Steatosis Than to Adipose Tissue Accumulation

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