Plasma Plasminogen Activator Inhibitor-1 Levels and Nonalcoholic Fatty Liver in Individuals With Features of Metabolic Syndrome

Larrañaga, Gabriela de; Wingeyer, Silvia Perés; Graffigna, Mabel; Belli, Susana; Bendezú, Karla; Álvarez, S. Escudero; Levalle, Oscar; Fainboim, Hugo

doi:10.1177/1076029607304094

Cited by 13 publications

(12 citation statements)

References 34 publications

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“…At variance with our results, after adjustment for covariates, only BMI and HDL-cholesterol remain predictors of PAI-1 levels, possibly due to differences in the characteristics of the two study population. Noteworthy, in that study, liver biopsy, performed on a subgroup of patients with chronically elevated transaminase levels, shows an association between insulin resistance and liver fibrosis [32].…”

Section: Discussionmentioning

confidence: 85%

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: Discussionmentioning

confidence: 85%

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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“…Emerging evidence suggests a critical role of apolipoproteins, including APOA4, in the pathogenesis of NAFLD Specifically, Kang et al demonstrated that over‐expression of APOA4 promotes lipid accumulation in the liver, and Qin et al reported that the level of APOA4 protein was increased in the genetically obese ( ob/ob ) mice. Furthermore, a marked upregulation of APOA4, as well as SERPINE1 and IGFBP1, has been demonstrated in patients with NAFLD.…”

Section: Discussionmentioning

confidence: 99%

“…In agreement with this, we identified several cancer‐related over‐expressed genes, including Cscbp2 , Apoa4 , Anxa2 , Serpine1 , Igfbp1 , and Tubb2a , that were associated with chromatin‐accessible regions in NASH‐derived HCC. It has been reported that up‐regulation of these genes may have significance in the hepatocarcinogenic process, in general, and in the pathogenesis of NAFLD and NAFLD‐associated liver carcinogenesis, in particular …”

Section: Discussionmentioning

confidence: 99%

Identification of chromatin‐accessible domains in non‐alcoholic steatohepatitis‐derived hepatocellular carcinoma

Dechassa

Tryndyak

Conti

et al. 2018

Molecular Carcinogenesis

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Non-alcoholic steatohepatitis (NASH) is becoming one of the major causes of hepatocellular carcinoma (HCC) in the United States and Western countries; however, the molecular mechanisms associated with NASH-related liver carcinogenesis are not well understood. In the present study, we investigated cancer-associated chromatin alterations using a model that resembles the development of NASH-related HCC in humans. An assay for transposase-accessible chromatin with high throughput sequencing (ATAC-seq) identified 1677 tumor-specific chromatin-accessible regions in NASH-derived HCC tissue samples. Using a combined analysis of ATAC-seq and global gene expression data, we identified 199 differentially expressed genes, 139 up-regulated and 60 down-regulated. Interestingly, 15 of the 139 up-regulated genes had accessible chromatin sites within 5 Kb of the transcription start site (TSS), including Apoa4, Anxa2, Serpine1, Igfbp1, and Tubb2a, genes critically involved in the development of NASH and HCC. We demonstrate that the mechanism for the up-regulation of these genes is associated with the enrichment of chromatin-accessible regions by transcription factors, especially NFATC2, and histone H3K4me1 and H3K27ac gene transcription-activating marks. These data underline the important role of chromatin accessibility perturbations in reshaping of the chromatin landscape in NASH-related HCC.

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“…A study by de Larrañaga et al in which adult patients at risk for metabolic syndrome underwent liver ultrasound scans to measure hepatic steatosis, concluded that plasma PAI-1 levels were better determined by whole-body fat content than liver steatosis content, after controlling for features of metabolic syndrome (28). Targher et al showed that in healthy adult men the association between ultrasound-diagnosed NAFLD and PAI-1 was no longer apparent after adjusting for CT-measured visceral adiposity (29).…”

Section: Discussionmentioning

confidence: 99%

Plasminogen Activator Inhibitor‐1 Predicts Quantity of Hepatic Steatosis Independent of Insulin Resistance and Body Weight

Holzberg¹,

Jin

et al. 2016

J. pediatr. gastroenterol. nutr.

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Objective To examine the association between PAI-1, an acute phase protein strongly associated with cardiovascular disease risk, and adiposity, insulin resistance, and inflammation among overweight and obese children with a wide range of hepatic steatosis. Methods Plasma PAI-1 levels were measured in a prospectively recruited cohort of 39 overweight or obese children who underwent comprehensive anthropometric assessment and metabolic measurements. Hepatic steatosis was quantified using magnetic resonance spectroscopy and participants were divided into 3 groups based on whether they had normal hepatic steatosis (<5%), low hepatic steatosis (≥5–10%) and high hepatic steatosis (>10%). Results Plasma PAI-1 levels significantly increased across the severity of hepatic steatosis in overweight and obese children, and this association was independent of BMI z-score, visceral fat, insulin resistance, and inflammatory markers (p < 0.05). Conclusion Hepatic steatosis in children is positively associated with circulating levels of PAI-1 independent of BMI, insulin resistance, and inflammatory markers. Further studies are needed to clarify the potential role of PAI-1 as a therapeutic target in pediatric NAFLD.

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Plasma Plasminogen Activator Inhibitor-1 Levels and Nonalcoholic Fatty Liver in Individuals With Features of Metabolic Syndrome

Cited by 13 publications

References 34 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

Identification of chromatin‐accessible domains in non‐alcoholic steatohepatitis‐derived hepatocellular carcinoma

Plasminogen Activator Inhibitor‐1 Predicts Quantity of Hepatic Steatosis Independent of Insulin Resistance and Body Weight

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