The rs1800470 Polymorphism of the TGFB1 Gene Is Associated with Myocardial Fibrosis in Heart Transplant Recipients.

The transforming growth factor ß1 (TGFß1), whose level may depend on the polymorphism of the TGFB1 gene, is involved in the formation of myocardial fibrosis. Myocardial fibrosis in a cardiac allograft may lead to a heart's structural and functional remodeling and subsequent dysfunction. The frequency of occurrence of alleles and genotypes of the TGFB1 gene polymorphic regions rs1800469, rs1800470, and rs1800471 in heart transplant recipients and their association with graft myocardial fibrosis were analyzed. Carriers of the CC genotype (p = 0.023, OR = 0.12, 95% CI: 0.017-1.0), and more often the G allele of rs1800471 (p = 0.023, OR = 7.76, 95% CI: 1.0-60.20), were found among heart transplant recipients less frequently than among healthy individuals. In patients with ischemic heart disease (IHD), the GG genotype was less common (p = 0.035, OR = 2.68, 95% CI: 1.061-6.793), while the A allele of rs1800469 was found more frequently (p = 0.035, OR = 0.37 95% CI: 0.148-0.942) than in patients with dilated cardiomyopathy (DCM). In heart transplant recipients with the AA genotype of rs1800470, myocardial fibrosis, verified by endomyocardial biopsy, was detected more often than in carriers of the G allele (OR = 10.4, 95% CI: 1.152-94.538, p = 0.013). The revealed differences suggest a relationship between TGFB1 gene polymorphism and graft myocardial fibrosis. Studies on a larger group of patients would make it possible to characterize the influence of genetic factors on the formation of myocardial fibrosis in heart transplant recipients.

[The relationship of level of transforming growth factor beta 1 with liver fibrosis in children with congenital diseases of hepatobilliary system.]

The article considers results of studying level of transforming growth factor beta 1 (TGF-ß1) in blood plasma of children with terminal stage of hepatic failure before and after transplantation of liver. The relationship of level of cytokine with degree of of liver fibrosis is analyzed. It is demonstrated that level of TGF-ß1 in blood plasma of children with hepatic failure is lower in comparison with healthy children and depends on degree of severity of liver fibrosis. Thus, level of cytokine in blood of patients is higher under fibrosis severity stage II and III, than under fibrosis of severity stage I and IV. After kindred transplantation of hepatic lobe, level of TGF-ß1in blood plasma of patients increases independently of initial degree of severity of fibrosis.

[Correction of cronic liver failure by transplantation of liver cells suspension and cell-engineering designs (experimental investigation)].

On an experimental model of chronic fibrotic liver damage (male rats Wistar (n-60), damage of CCl4, the duration of the experiment 90 days) it was studied the effectiveness of cell therapy for the correction of chronic liver failure. These rats were divided into 3 experimental groups: in the Ist-group (control, n=10) isotonic saline (650 mkl.) was injected; in the IInd-group (n=20) suspension of liver cells was applicated in a dose 8 - l0 x 10(6) cells; in the IIIrd-group (n=30) suspension of liver cells and bone marrow cells (mesenchymal stromal cells) in ratio 5:1 were used as cell associates on microparticles intjectable heterogeneous biopolymer hydrogel "SpheroGEL" (cell-engineering design) in common dose 8 - l0 x 10(6) It was ascertained that in the 2nd and in the 3rd groups the accelerated normalization of disturbed liver functional indices (ALT, AST, ALP) took place - to 30 days, but in the control group only to 90 days. The reliable differences in rats ofnormalization offunctional indices were absent between the IInd and the IIIrd groups. But in 90 days by using special histological dyeing it was found out that defibrotic processes in liver tissue were more expressed in the IIIrd group in comparison with the IIIrd group. Received results were consequence of prolonged vital activity of cells (liver cells and mesenchymal stromal bone marrow cells) into cell-engineering designs, which were transplanted in the IIIrd group. The obtained effect can be explained by that the developed cell-engineering designs provide adequate conditions for prolonged vital activity of the transplanted cells.