210, p=0.007; r2=0.113, p=0.03), this relationship was not observed in the HCV-infected patients (r2=0.040, p=0.20; fda approved r2=0.046, p=0.33). Finally, no differences in either HMOX activity or HMOX expression between SVR and non-SVR patients were detected. Correlation between BLVRA and HMOX mRNA Levels in the Liver and PBL, and HCV RNA in PBL and Liver Tissue No significant differences in pretreatment expression of BLVRA in the liver were found between SVR (n=18) and non-SVR patients (n=4) (0.35��0.24 vs. 0.34��0.24 p=0.97) most likely because of high variability of BLVRA expression in the liver compared to PBL. BLVRA expression, but not that of HMOX1/HMOX2, in the liver and PBL of HCV-infected patients were in direct relationship (n=13, r2=0.347, p=0.03).
No correlation was found between the mRNA levels of HMOX1/HMOX2/BLVRA and HCV RNA in the liver and PBL. Discussion Because of the side effects and high costs of current antiviral therapy, it is very important to identify those markers that can discriminate among those patients who will respond to the standard treatment. The precise molecular mechanisms underlying the responsiveness to antiviral treatment among HCV-infected individuals have yet to be completely identified. Enzymes of the heme catabolic pathway seem to belong to such promising markers. In fact, Zhu and coworkers [32] recently provided a plausible mechanism for the antiviral activity of HMOX1, demonstrating that the direct product of its activity, biliverdin, potently inhibits viral replication at biologically relevant concentrations in human hepatoma Huh-7.
5 cells replicating HCV RNA, most likely via inhibition of HCV NS3/4A protease. In the current study, we prospectively investigated HMOX activity, as well as HMOX1 expression in HCV-infected patients. Surprisingly, no difference in mRNA expression of HMOX1 in PBL was found between therapeutically na?ve HCV patients and controls, although the total HMOX activity in PBMC was significantly decreased in HCV patients before treatment, compared to the control group. Furthermore, a correlation between the expression of HMOX1, HMOX2, and total HMOX activity was only detected in the control samples; not in the HCV-infected patients. In fact, interference of HCV with HMOX1 induction [33], reduced hepatic expression of HMOX1 both in vitro and in vivo in HCV infection [8]; additionally, induced hepatic HMOX1 expression in vitro were reported [17].
We hypothesized that HMOX and BLVRA gene expression in PBL can reflect their expression in the liver. In our study, due to unavailability of liver specimens of control subjects, correlation between the liver and PBL could be analyzed only in HCV patients. No association of HMOX1/HMOX2 expression was Carfilzomib found between the liver and PBL, and HMOX1/HMOX2/BLVRA and HCV RNA in the liver and PBL.