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Cardiac fibrotization is a well-known process characteristic of many cardiac pathological conditions. The key element is excessive activation of cardiac fibroblasts, their transdifferentiation into myofibroblasts, increased production, and accumulation of extracellular matrix proteins, resulting in cardiac stiffness. The exact cellular mechanisms and molecular components involved in the process are not fully elucidated, but the SOCE mechanism could play an important role. Its key molecules are the molecular sensor of calcium in ER/SR - STIM and the highly selective calcium channels Orai located in the plasma membrane. This study aims to evaluate selected SOCEassociated genes in the activation of HCF cell culture by several known substances (phenylephrine, isoprenaline) that represent cardiovascular overload. After cell cultivation, cell medium was collected to measure the soluble collagen content. From the harvested cells, qRT-PCR was performed to determine the mRNA levels of the corresponding genes. The activation of cells was based on changes in the relative expression of collagen genes as well as the collagen content in the medium of the cell culture. We detected an increase in the expression of the Orai2 isoform, a change in the Orai1/Orai3 ratio and also an increase in the expression of the STIM2 isoform. These results suggest an increased activation of the SOCE mechanism under stress conditions of fibroblasts, which supports the hypothesis of fibroblast activation in pathological processes by altering calcium homeostasis through the SOCE mechanism. [ABSTRACT FROM AUTHOR]

Currently published data suggest that the specific transcription factors GATA4 and MEF2C play a crucial role in the development of pathological cardiac hypertrophy. The synergistic effect of these two transcription factors was observed mainly with a calcineurin/NFAT signalling pathway that induces the expression of genes associated with hypertrophy. It is assumed that statins can affect the process of cardiac fibrosis and subsequent heart remodelling through cardioprotective pleiotropic effects, which are still not sufficiently examined. The aim of the study was to investigate the intervention of atorvastatin into molecular mechanisms of cardiac fibrosis and pathological cardiac hypertrophy by monitoring changes of the expression of selected genes in human cardiac fibroblasts (HCF) in vitro. Experimental cell cultures of HCF were treated with atorvastatin (10 µM) for 24 hr, 48 hr, and 72 hr. Changes in the expression of selected genes were assessed by RT-qPCR. Our findings reflect the occurrence of several changes in HCF after their treatment with atorvastatin. A significant reduction (p < .0001) was observed in the gene expression of the alpha-SMA, a major marker of the activated fibroblasts responsible for development of cardiac fibrosis. A significant decrease (p < .05) in gene expression of the transcription factors GATA4 and MEF2C was also observed, demonstrating a possible protective effect of atorvastatin against pathological cardiac hypertrophy. [ABSTRACT FROM AUTHOR]