OBJECTIVE

To assess the relationship between inflammatory and metabolic processes in cultured human cardiomyocytes and myocardium of patients with dilated cardiomyopathy (DCM) and heart failure (HF).

MATERIAL AND METHODS

We studied endomyocardial biopsy specimens obtained from interventricular septum in patients with DCM (n=12). As a control, autopsy material of the left ventricular myocardium of a person without cardiovascular diseases (n=5) was used. Cardiomyocyte cultures obtained from human fetal hearts at 8—9 weeks of gestation (n=3) were used for studies in vitro. Markers of lymphocytes CD4 and CD8 were determined in myocardial tissue by immunofluorescent method. In the same myocardial samples and cultured cardiomyocytes, real-time PCR was used to detect expression of PPARα (peroxisome proliferator-activated receptor alpha) and its target genes LCAD (long-chain acyl-CoA dehydrogenase), CPT-1 (carnitine palmitoyl transferase-1) and CD36 (FAT) (fatty acid transporter).

RESULTS

Using a cellular model of induced inflammation, we revealed that treatment with TNF-alpha for 4 and 24 hours reduces expression of PPAR-alpha and changes expression of target genes. At the same time, treatment for 48 hours increases expression of the main regulator of cardiac metabolism PPAR-alpha and its target genes. These data allow us to speak about the relationship between inflammatory and metabolic pathways in cardiomyocytes. We found the changes in expression of PPAR-alpha and its target genes in patients with DCM and HF. Infiltration of CD4 and CD8 tissue by lymphocytes in myocardium of the same patients indicates inflammatory processes.

CONCLUSION

Identified inflammatory processes in patients with DCM and HF, as well as data obtained on cardiomyocyte cultures suggest that inflammation may contribute to metabolic changes in DCM patients with HF, but this issue requires further study.