Expression of apolipoprotein M in human hepatocellular carcinoma tissues

BackgroundHepatitis virus B (HBV) has infected millions of people worldwide. Notably, such infections can be associated with hepatic complications. Levels of apolipoprotein M (apoM), a component of high-density lipoprotein (HDL), are known to be significantly elevated in patients with chronic hepatitis B (CHB). The aim of this study was to investigate the relationship between HBV DNA load in serum and serum apoM levels in patients with CHB.MethodsA total of 73 HBeAg-negative CHB patients, 50 HBeAg-positive CHB patients, and 79 non-CHB controls were included in the study cohort. The age and body mass index (BMI) of the study participants were matched. Serum levels of apoM and the HBV antigens HBsAg and HBeAg were measured by enzyme-linked immunosorbent assay (ELISA) analysis. Serum levels of alanine aminotransferase (ALT), aspartate transaminase (AST), cholesterol, and triglycerides (TG) were assessed using an automatic biochemical analyzer. Serum HBV DNA levels were quantified by real-time PCR analysis. Data were analyzed by Spearman’s rank correlation coefficient, Pearson correlation coefficient, and multivariate linear regression model (continuous variables), or Student’s t-test (mean differences).ResultsBoth the HBeAg-negative CHB and HBeAg-positive CHB patient groups exhibited elevated serum levels of apoM. Moreover, serum apoM levels were positively correlated with serum HBV DNA levels in HBeAg-negative CHB patients (r = 0.394, p < 0.001). Conversely, there was no significant relationship between apoM and HBV DNA levels in the HBeAg-positive CHB group (r = 0.197, p = 0.170). The median log copies/mL value for HBV DNA (4.00) was considered the cutoff point for the HBeAg-negative CHB group. Notably, a significant number of patients with HBV DNA levels above the cutoff point also had higher serum apoM levels (63.38 ± 29.84 vs. 41.41 ± 21.84; p = 0.001).ConclusionsOur findings reveal that the correlation between serum apoM levels and viral loads may depend on HBeAg status, as serum apoM levels were positively correlated with HBV DNA levels in HBeAg-negative CHB patients. These results suggest that HBeAg may play a role in apoM-related lipid metabolism and anti-inflammatory functions in hepatitis B patients. Thus, our findings may facilitate the clinical management of HBV infection.

Section: Discussionsupporting

confidence: 93%

“…Previous studies reported that chronic hepatitis patients exhibit higher serum apoM levels than healthy control subjects [11, 12]. Similarly, HepG2 cells transfected with an infectious HBV clone were found to express significantly higher levels of apoM mRNA and protein than uninfected HepG2 cells in vitro.…”

Section: Introductionmentioning

confidence: 84%

Positive association between serum apolipoprotein M levels and hepatitis B virus DNA load in HBeAg-negative chronic hepatitis B

Shen

et al. 2016

“…It has been reported that the plasma apoM levels were higher in the patients suffered from HCC and other chronic liver diseases than in normal subjects[28,29]. Our result is in line with earlier results from experiment based on semiquantitatively determined by both dot-blotting and western blotting analysis[29]. However, we didn't find any correlation between HBV viral load and ApoM levels.…”

Section: Discussionsupporting

confidence: 91%

Enchanced levels of apolipoprotein M during HBV infection feedback suppresses HBV replication

Zhu

Cheng

et al. 2011

BackgroundChronic liver diseases can interfere with hepatic metabolism of lipoproteins, apolipoproteins. Hepatitis B virus (HBV) is a major etiological agent causing acute and chronic liver diseases. Apolipoprotein M (ApoM) is a high-density lipoprotein (HDL) apolipoprotein and exclusively expressed in the liver parenchyma cells and in the tubular cells of the kidney. This study was to determine the correlation between HBV infection and ApoM expression.Materials and methodsSerum ApoM levels in patients with HBV infection and in healthy individuals were measured by ELISA, ApoM mRNA expression were determined by RT-PCR, and the expression of S and E proteins of HBV, as well as the synthesis of viral DNA were measured by ELISA and real-time PCR.ResultsThe levels of serum ApoM was significantly elevated in patients as compared to healthy individuals (P < 0.001), ApoM promoter activity, mRNA and protein expression were all stimulated in cells transfected with infectious HBV clone. In addition, ApoM decreases the expression of S and E proteins of HBV and the synthesis of viral DNA.ConclusionRaised ApoM levels in HBV infection may in turn suppress HBV replication, one of the protective mechanisms of nature.

“…Recent observations strongly suggest that apoM is predominantly confined to the HDL particles in human plasma and it may have antiatherogenic properties involving in the conversion of large HDL to pre-β HDL, the later mainly functions as an acceptor of peripherally deposited cholesterol that is described as the revise cholesterol transportation [9,17]. Moreover other researches indicated that apoM might be also involved in the immunity, inflammation, and neoplasia [18-20]. However, the physio-pathological functions of apoM are still not fully revealed.…”

Section: Discussionmentioning

confidence: 99%

TO901317 regulating apolipoprotein M expression mediates via the farnesoid X receptor pathway in Caco-2 cells

Zhu¹,

Di²,

Zhang³

et al. 2011

Self Cite

BackgroundApolipoprotein M (apoM) may have potential antiatherosclerotic properties. It has been reported that apoM expression could be regulated by many intracellar and extracellar factors. In the present study we further investigated regulation of apoM expression in Caco-2 cells stimulated by a liver X receptor (LXR) agonist, TO901317.Materials and methodsCaco-2 cells were cultured in the presence of either TO901317, farnesoid X receptor (FXR) antagonist guggulsterone or TO901317 together with guggulsterone at different concentrations for 24 hrs. The mRNA levels of ATP-binding cassette transporter A1 (ABCA1), apoA1, apoM, liver receptor homologue-1 (LRH-1) and short heterodimer partner 1 (SHP1) were determined by real-time RT-PCR.ResultsWhen Caco-2 cell cultured with TO901317 alone, the mRNA levels of ABCA1, apoA1, apoM, LRH-1 and SHP1 were significantly increased with dose-dependent manners (p < 0.05), whereas when the cells cultured with guggulsterone alone, the mRNA levels of apoM, SHP1 and LRH-1 (p < 0.05) were strongly inhibited. Moreover, guggulsterone could abolish the TO901317 enhanced mRNA levels of apoA1 apoM, SHP1 and LRH-1.ConclusionThe present study demonstrated that LXR agonist TO901317 induced apoM expression in Caco-2 cells might be mediated via the LXR/FXR pathway.