ABSTRACT
BACKGROUND: The severity of pulmonary arterial hypertension (PAH) is classified based on mean pulmonary artery pressure (mPAP) levels. However, other markers have not been elucidated. Fibrinolytic markers, such as total plasminogen activator inhibitor-1 (tPAI-1) and thrombomodulin (TM), are known to reflect arterial endothelial function. However, the relationship between serum tPAI-1, TM and pulmonary circulation has not been completely determined. METHODS: This study included 100 consecutive patients (38 men), with a mean age of 68.9 ± 12.0 years, with cardiac diseases who underwent right heart catheterization. Serum coagulation and fibrinolytic marker levels were measured. RESULTS: The average mPAP value was 25.1 ± 13.1 mmHg for all patients. The mPAP levels revealed a significant positive correlation with serum tPAI-1 (ρ = 0.24, p = 0.042) and uric acid (ρ = 0.29, p = 0.0031) levels. In the group with mPAP levels less than 25 mmHg (n = 58, ave. 17.3 ± 4.3 mmHg), mPAP levels showed a significant positive correlation with serum tPA-1 (ρ = 0.34, p = 0.034) and TM (ρ = 0.34, p = 0.043) values. The mean tPAI-1 (29.8 ± 23.3 ng/ml, p = 0.047) and uric acid (5.7 ± 1.8 mg/dl, p = 0.026) levels were significantly less in those with lower mPAP levels. A multivariate analysis revealed that tPAI-1 alone was a significant independent characteristic marker of PAH (odds ratio 1.02, 95%CI 1.000-1.036, p = 0.034). CONCLUSIONS: These results indicate that serum tPAI-1 and TM may be useful predictors of severity, similar to mPAP in patients with PAH. They could be beneficial in predicting PAH among patients in the early stage of the disease.
ABSTRACT
BACKGROUND: Polychlorinated biphenyls (PCBs) are persistent environmental pollutants that are detectable in the serum of all American adults. Amongst PCB congeners, PCB 153 has the highest serum level. PCBs have been dose-dependently associated with obesity, metabolic syndrome and nonalcoholic fatty liver disease (NAFLD) in epidemiological studies. OBJECTIVE: The purpose of this study is to determine mechanisms by which PCB 153 worsens diet-induced obesity and NAFLD in male mice fed a high-fat diet (HFD). METHODS: Male C57BL6/J mice were fed either control or 42% milk fat diet for 12 weeks with or without PCB 153 coexposure (50 mg/kg ip ×4). Glucose tolerance test was performed, and plasma and tissues were obtained at necropsy for measurements of adipocytokine levels, histology and gene expression. RESULTS: In control diet-fed mice, addition of PCB 153 had minimal effects on any of the measured parameters. However, PCB 153 treatment in high-fat-fed mice was associated with increased visceral adiposity, hepatic steatosis and plasma adipokines including adiponectin, leptin, resistin and plasminogen activator inhibitor-1 levels. Likewise, coexposure reduced expression of hepatic genes implicated in ß-oxidation while increasing the expression of genes associated with lipid biosynthesis. Regardless of diet, PCB 153 had no effect on insulin resistance or tumor necrosis factor alpha levels. CONCLUSION: PCB 153 is an obesogen that exacerbates hepatic steatosis, alters adipocytokines and disrupts normal hepatic lipid metabolism when administered with HFD but not control diet. Because all US adults have been exposed to PCB 153, this particular nutrient-toxicant interaction potentially impacts human obesity/NAFLD.