Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012;7(2):e31799.
doi: 10.1371/journal.pone.0031799. Epub 2012 Feb 16.

Decreased circulating endothelial progenitor cell levels and function in patients with nonalcoholic fatty liver disease

Chia-Hung Chiang  1 , Po-Hsun Huang, Fa-Po Chung, Zu-Yin Chen, Hsin-Bang Leu, Chin-Chou Huang, Tao-Cheng Wu, Jaw-Wen Chen, Shing-Jong Lin
Affiliations

Decreased circulating endothelial progenitor cell levels and function in patients with nonalcoholic fatty liver disease

Chia-Hung Chiang et al. PLoS One. 2012.

Abstract

Objectives: Nonalcoholic fatty liver disease (NAFLD) is associated with advanced atherosclerosis and a higher risk of cardiovascular disease. Increasing evidence suggests that injured endothelial monolayer is regenerated by circulating bone marrow derived-endothelial progenitor cells (EPCs), and levels of circulating EPCs reflect vascular repair capacity. However, the relation between NAFLD and EPC remains unclear. Here, we tested the hypothesis that patients with nonalcoholic fatty liver disease (NAFLD) might have decreased endothelial progenitor cell (EPC) levels and attenuated EPC function.

Methods and results: A total of 312 consecutive patients undergoing elective coronary angiography because of suspected coronary artery disease were screened and received examinations of abdominal ultrasonography between July 2009 and November 2010. Finally, 34 patients with an ultrasonographic diagnosis of NAFLD, and 68 age- and sex-matched controls without NAFLD were enrolled. Flow cytometry with quantification of EPC markers (defined as CD34(+), CD34(+)KDR(+), and CD34(+)KDR(+)CD133(+)) in peripheral blood samples was used to assess circulating EPC numbers. The adhesive function, and migration, and tube formation capacities of EPCs were also determined in NAFLD patients and controls. Patients with NAFLD had a significantly higher incidence of metabolic syndrome, previous myocardial infarction, hyperuricemia, and higher waist circumference, body mass index, fasting glucose and triglyceride levels. In addition, patients with NAFLD had significantly decreased circulating EPC levels (all P<0.05), attenuated EPC functions, and enhanced systemic inflammation compared to controls. Multivariate logistic regression analysis showed that circulating EPC level (CD34(+)KDR(+) [cells/10(5) events]) was an independent reverse predictor of NAFLD (Odds ratio: 0.78; 95% confidence interval: 0.69-0.89, P<0.001).

Conclusions: NAFLD patients have decreased circulating EPC numbers and functions than those without NAFLD, which may be one of the mechanisms to explain atherosclerotic disease progression and enhanced cardiovascular risk in patients with NAFLD.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Representative flow cytometry analysis for quantifying the number of circulating endothelial progenitor cells (EPCs).
Upper left shows mononuclear cells (MNCs) were gated by forward/sideward scatter (FSC/SSC) in patients with nonalcoholic fatty liver disease (NAFLD) (A) and without NAFLD (B). The numbers of circulating EPCs were defined as CD34+, CD34+KDR+, and CD34+KDR+CD133+, respectively.
Figure 2
Figure 2. The association between EPC levels (% and cells/105 events) and the severity of non-alcoholic fatty liver disease (values presented as means ± standard error; FL, fatty liver; Mild, mild fatty liver; Moderate, moderate fatty liver; Severe, severe fatty liver).
Figure 3
Figure 3. Morphology and characterization of human endothelial progenitor cells (EPCs) from peripheral blood.
Peripheral blood mononuclear cells (MNCs) were plated on a fibronectin-coated culture dish on the first day (A). Four days after plating, adherent early EPCs with a spindle shape were shown (B). Three weeks after plating, late EPCs with a cobblestone-like morphology were selected, reseeded, and grown to confluence (C). Early and late EPC characterization were performed by flow cytometry analysis (CD45) and immunohistochemical staining. Most of the EPC expressed endothelial and hematopoietic stem cell markers, VE-cadherin, PECAM-1 (CD31), CD34, KDR, and AC133 (Figure 3), which are considered critical markers of EPCs. Cells were counterstained with 4′,6-diamidino-2-phenylindole (DAPI) for the nuclei (blue).
Figure 4
Figure 4. Comparison of the EPC adhesive function (A), migration (B), and tube formation capacities (C) in subjects with or without fatty liver (values presented as means ± SD; HPF: high-power field; *P<0.05).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Adams LA, Angulo P. Recent concepts in non-alcoholic fatty liver disease. Diabet Med. 2005;22(9):1129–1133. - PubMed
    1. Lonardo A, Bellini M, Tartoni P, Tondelli E. The bright liver syndrome. Prevalence and determinants of a “bright” liver echopattern. Ital J Gastroenterol Hepatol. 1997;29(4):351–356. - PubMed
    1. el-Hassan AY, Ibrahim EM, al-Mulhim FA, Nabhan AA, Chammas MY. Fatty infiltration of the liver: analysis of prevalence, radiological and clinical features and influence on patient management. Br J Radiol. 1992;65(777):774–778. - PubMed
    1. Fan JG, Zhu J, Li XJ, Li L, Dai F, et al. Prevalence of and risk factors for fatty liver in a general population of Shanghai, China. J Hepatol. 2005;43(3):508–514. - PubMed
    1. Tarantino G, Saldalamacchia G, Conca P, Arena A. Non-alcoholic fatty liver disease: further expression of the metabolic syndrome. J Gastroenterol Hepatol. 2007;22(3):293–303. - PubMed

Publication types