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Abstract. Idiopathic pulmonary arterial hypertension (IPAH)is characterized by smooth muscle cell, endothelial cell, and fibroblast hypertrophy and an increase in extracellular matrix volume in pulmonary precapillary arterioles. These features lead to a gradual increase of pulmonary vascular resistance, right-heart failure, and premature death. Bone morphogenetic protein receptor type 2 (BMPR-2) gene mutations have been identified to cause IPAH. BMPR-2 receptor mutation results in BMP signalling pathway termination and leads to disturbed growth and differentiation of pulmonary circulation cells. Transforming growth factor (TGF)-ß1 inhibits the migration and proliferation of endothelial and smooth muscle cells, and stimulates their differentiation, thus it has antiinflammatory and immunosuppressive properties, inhibiting vascular remodeling and is responsible for extracellular matrix production. The aim of this study was to analyse the profile of TGF-ß1 and the expression of its receptor (TßR I, TßR II and TßR III-betaglycan) genes in IPAH and in secondary forms of pulmonary arterial hypertension [Eisenmenger's syndrome (ES) patients]. Twenty-one patients with IPAH (2 men), 12 ES patients, and 10 healthy controls were enrolled in the study. QRT-PCR analysis of the transcriptive activity of TGF-ß1 and its receptor genes was performed with each patient. There were differences in receptor gene expression among the patient groups. The highest expression was observed in Eisenmenger syndrome patients (approximately 5-to 8-fold increase). There was a negative correlation between the gene expression of TGF-ß1 and that of its receptors, and a positive correlation between TßR II and TßR III in healthy controls. In IPAH patients a positive correlation between TGF-ß1 and TßR I was found. There was a difference in expression of TGF-ß1/receptor gene ratios and expression of receptor gene ratios between the examined groups. The differences in expression between IPAH and ES patients might suggest the role of these cytokines in IPAH pathogenesis. A disturbed proportion of expression of TGF-ß1 and receptor genes in IPAH patients might be one of the pathogenetic factors of the disease.

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Pterostilbene is a dietary phytochemical that has been found to possess several biological activities, such as antioxidant and anti-inflammatory. Recent studies have shown that it exhibits the hallmark characteristics of an anticancer agent. The aim of the study was to investigate the anticancer activity of pterostilbene against HT-29 human colon cancer cells, focusing on its influence on cell growth, differentiation, and the ability of this stilbene to induce cell death. To clarify the mechanism of pterostilbene activity against colon cancer cells, changes in the expression of several genes and proteins that are directly related to cell proliferation, signal transduction pathways, apoptosis, and autophagy were also evaluated. Cell growth and proliferation of cells exposed to pterostilbene (5–100 µM) were determined by SRB and BRDU assays. Flow cytometric analyses were used for cell cycle progression. Further molecular investigations were performed using quantitative real-time RT-PCR. The expression of the signaling proteins studied was determined by the ELISA method. The results revealed that pterostilbene inhibited proliferation and induced the death of HT-29 colon cancer cells. Pterostilbene, depending on concentration, caused inhibition of proliferation, G1 cell arrest, and/or triggered apoptosis in HT-29 cells. These effects were mediated by the down-regulation of the STAT3 and AKT kinase pathways. It may be concluded that pterostilbene could be considered as a potential therapeutic option in the treatment of colon cancer in the future.

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