Abstract
Objectives
We evaluated circulating levels of biomarkers of atherosclerosis (soluble intercellular
adhesion molecule: sICAM-1, plasminogen activator inhibitor: PAI-1 and soluble CD40
ligand: sCD40L) in patients with NAFLD proven through biopsy and control subjects,
and correlated them with the histological disease severity. We further explored liver
protein expression of ICAM-1, CD40 and PAI-1 in patients with different histological
forms of NAFLD and control liver biopsies.
Patients and methods
We included 215 individuals: 113 patients with NAFLD (simple steatosis n = 45 and NASH n = 68) and 102 control subjects. Circulating levels of the biomarkers were measured by
ELISA. Liver expression of ICAM-1, CD40 and PAI-1 was assessed by immunohistochemistry
using monoclonal antihuman antibodies.
Results
Patients with NAFLD, in comparison with control subjects, showed significantly higher
circulating levels of sICAM-1 (605.3 ± 34.6 ng/ml vs. 356.5 ± 24.6 ng/ml, p = 5.9 × 10−6), PAI-1 (22.8 ± 1.7 ng/ml vs. 19.0 ± 2.1 ng/ml, p = 0.0149) and sCD40L (1347.5 ± 513.7 pg/ml vs. 804.5 ± 396.1 pg/ml, p = 0.0229), results expressed as mean ± SE. sICAM-1 was a strong predictor of histological severity of NAFLD, after adjusting
for potential confounders. In addition, patients with NAFLD showed significantly higher
liver staining scores for ICAM-1 and PAI-1 than control liver biopsies. ICAM-1 immunoreactivity
in lobular inflammatory infiltrate showed high scores in NASH patients; a significant
correlation was found between both the degree of liver steatosis and the severity
of necroinflammatory activity and liver ICAM-1 expression.
Conclusions
Our study shows that NAFLD is associated with elevated circulating levels and abnormal
liver expression of molecular mediators of atherosclerosis. Additionally, ICAM-1 may
be involved in liver damage and inflammation.
Abbreviations:
NAFLD (nonalcoholic fatty liver disease), NASH (nonalcoholic steatohepatitis), PAI-1 (plasminogen activator inhibitor-1), sICAM-1 (soluble intercellular adhesion molecule-1), sCD40L (soluble CD40 ligand), ELISA (enzyme-linked immuno-sorbent assay)Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to AtherosclerosisAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Nonalcoholic fatty liver disease: a feature of the metabolic syndrome.Diabetes. 2001; 50: 1844-1850
- Increased risk of cardiovascular disease in non-alcoholic fatty liver disease: causal effect or epiphenomenon?.Diabetologia. 2008; 51: 1947-1953
- Non-alcoholic fatty liver disease is strongly associated with carotid atherosclerosis: a systematic review.J Hepatol. 2008; 49: 600-607
- Evaluation of vulnerable coronary plaques and non-alcoholic fatty liver disease (NAFLD) by 64-detector multislice computed tomography (MSCT).Circ J. 2008; 72: 618-625
- Endothelial dysfunction and cardiovascular risk profile in nonalcoholic fatty liver disease.Hepatology. 2005; 42: 473-480
- Non-alcoholic fatty liver disease and increased risk of cardiovascular disease.Atherosclerosis. 2007; 191: 235-240
- Systemic inflammation in nonalcoholic fatty liver disease is characterized by elevated levels of CCL2.J Hepatol. 2006; 44: 1167-1174
- NASH predicts plasma inflammatory biomarkers independently of visceral fat in men.Obesity (Silver Spring). 2008; 16: 1394-1399
- Increased hepatic and circulating interleukin-6 levels in human nonalcoholic steatohepatitis.Am J Gastroenterol. 2008; 103: 1372-1379
- High-sensitivity C-reactive protein is an independent clinical feature of nonalcoholic steatohepatitis (NASH) and also of the severity of fibrosis in NASH.J Gastroenterol. 2007; 42: 573-582
- Serum intercellular adhesion molecule-1 in patients with nonalcoholic steatohepatitis: comparison with alcoholic hepatitis.Alcohol Clin Exp Res. 2007; 31: S83-S87
- Cytokines in alcoholic and nonalcoholic steatohepatitis.N Engl J Med. 2000; 343: 1467-1476
- Cross-sectional study of soluble intercellular adhesion molecule-1 and cardiovascular risk factors in apparently healthy men.Arterioscler Thromb Vasc Biol. 1999; 19: 1595-1599
- Requirement for CD154 in the progression of atherosclerosis.Nat Med. 1999; 5: 1313-1316
- High plasminogen activator inhibitor and tissue plasminogen activator levels in plasma precede a first acute myocardial infarction in both men and women: evidence for the fibrinolytic system as an independent primary risk factor.Circulation. 1998; 98: 2241-2247
- Design and validation of a histological scoring system for nonalcoholic fatty liver disease.Hepatology. 2005; 41: 1313-1321
- Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions.Am J Gastroenterol. 1999; 94: 2467-2474
- Nonalcoholic steatohepatitis: summary of an AASLD single topic conference.Hepatology. 2003; 37: 1202-1219
- Significant gene expression differences in histologically “normal” liver biopsies: implications for control tissue.Hepatology. 2008; 48: 953-962
- Fatty liver: a novel component of the metabolic syndrome.Arterioscler Thromb Vasc Biol. 2008; 28: 27-38
- Long-term follow-up of patients with NAFLD and elevated liver enzymes.Hepatology. 2006; 44: 865-873
- Plasma PAI-1 levels are increased in patients with nonalcoholic steatohepatitis.Diabetes Care. 2007; 30: e31-e32
- Nonalcoholic fatty liver disease and risk of future cardiovascular events among type 2 diabetic patients.Diabetes. 2005; 54: 3541-3546
- Is the intercellular adhesion molecule-1/leukocyte function associated antigen 1 pathway of leukocyte adhesion involved in the tissue damage of alcoholic hepatitis?.Gut. 1992; 33: 268-271
- Serum intercellular adhesion molecule-1 in alcoholic liver disease and its relationship with histological disease severity.J Hepatol. 1997; 26: 280-286
- Plasma PAI-1 levels are more strongly related to liver steatosis than to adipose tissue accumulation.Arterioscler Thromb Vasc Biol. 2003; 23: 1262-1268
- Losartan reduces liver expression of plasminogen activator inhibitor-1 (PAI-1) in a high fat-induced rat nonalcoholic fatty liver disease model.Atherosclerosis. 2009; 206: 119-126
- Nonalcoholic fatty liver disease in humans is associated with increased plasma endotoxin and plasminogen activator inhibitor 1 concentrations and with fructose intake.J Nutr. 2008; 138: 1452-1455
- CD40L proinflammatory and profibrotic effects on proximal tubular epithelial cells: role of NF-kappaB and lyn.J Am Soc Nephrol. 2006; 17: 627-636
- CD40 and CD154 in cell-mediated immunity.Annu Rev Immunol. 1998; 16: 111-135
- CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells.Nature. 1998; 391: 591-594
Article info
Publication history
Published online: November 06, 2009
Accepted:
October 5,
2009
Received in revised form:
September 1,
2009
Received:
July 31,
2009
Identification
Copyright
© 2009 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
