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Altered Expression of ORAI and STIM Isoforms in Activated Human Cardiac Fibroblasts
R Čendula1, N Chomaničová, A Adamičková
1Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovak republic. matus@fpharm.uniba.sk.
Physiological Research
|December 17, 2021
Summary
This study reveals that the store-operated calcium entry (SOCE) mechanism, involving STIM and Orai proteins, is activated in cardiac fibroblasts under stress. This activation may contribute to pathological cardiac fibrotization by altering calcium homeostasis.
Area of Science:
- Cardiovascular Biology
- Cellular Physiology
- Molecular Medicine
Background:
- Cardiac fibrotization, characterized by fibroblast activation and extracellular matrix accumulation, leads to cardiac stiffness in various heart conditions.
- The precise cellular mechanisms driving fibrotization are not fully understood, but store-operated calcium entry (SOCE) is a potential key pathway.
- SOCE involves stromal interaction molecule (STIM) proteins sensing calcium levels in the endoplasmic reticulum and Orai channels mediating calcium influx.
Purpose of the Study:
- To investigate the role of SOCE-associated genes in human cardiac fibroblast (HCF) activation.
- To evaluate the impact of cardiovascular overload stimuli (phenylephrine, isoprenaline) on SOCE components in HCFs.
- To determine if altered calcium homeostasis via SOCE contributes to pathological cardiac fibrotization.
Main Methods:
- Human cardiac fibroblast (HCF) cell cultures were treated with phenylephrine and isoprenaline to simulate cardiovascular overload.
- Soluble collagen content in the cell medium was measured to assess fibroblast activation.
- Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to determine mRNA levels of SOCE-associated genes (STIM, Orai isoforms).
Main Results:
- Increased expression of the Orai2 isoform was observed in activated HCFs.
- A significant change in the Orai1/Orai3 expression ratio was detected.
- STIM2 isoform expression also increased, suggesting heightened SOCE activity under stress conditions.
- Elevated collagen production correlated with these gene expression changes.
Conclusions:
- The study provides evidence for increased SOCE mechanism activation in cardiac fibroblasts under simulated stress conditions.
- Altered expression of STIM and Orai isoforms suggests a critical role for calcium dysregulation in fibroblast activation.
- These findings support the hypothesis that SOCE-mediated calcium influx is a key factor in pathological cardiac fibrotization.
