Calcyclin-binding protein/Siah-1-interacting protein (CacyBP/SIP) is the recently discovered peptide, which participates in various intracellular processes. Recent reports indicated that CacyBP/SIP activates the ubiquitin ligases and promotes proteasomal degradation of proteins. One of the most important proteins degraded in CacyBP/SIP-dependent pathway is β-catenin. Considering the key importance of β-catenin in the functioning of the cardiovascular system and in the view of the close relationship between CacyBP/SIP, β-catenin, and proteasomal activity, we have decided to undertake research to identify and evaluate the distribution of CacyBP/SIP, β-catenin and the LMP7 subunit of the immunoproteasome in the heart of rats with hypertension of various etiology. The studies were carried out on the hearts of rats with spontaneous hypertension (SHR), renovascular hypertension, and DOCA-salt hypertension. The myocardial expression of CacyBP/SIP, β-catenin, and LMP7 was detected by immunohistochemistry using the EnVision method. The hypertension significantly increased the immunoreactivity to CacyBP/SIP and LMP-7, while weakening the β-catenin immunoreaction. The intensity of the observed changes depends on the type of hypertension. Our results show an innovative and important network of interactions between proteins potentially involved in the development and progression of heart problems in various types of hypertension. This report might contribute to deeper understanding of the role of the CacyBP/SIP protein, β-catenin, and immunoproteasomes in heart function, as well as to bringing new information concerning pathophysiologic mechanisms leading to cardiac dysfunction in the state of elevated blood pressure.
Impact statement: Despite extensive research into the pathogenesis of hypertension and disease-related end organ damage, the mechanisms leading to cardiac complications of hypertensive patients are still not fully elucidated. The aim of the presented research was immunodetection and evaluation of CacyBP/SIP, β-catenin, and proteasomes in the hearts of rats with hypertension of different etiology. Our results show an innovative and important network of interactions between proteins potentially involved in the development and progression of heart problems in various types of hypertension. This report might contribute to deeper understanding of the role of the CacyBP/SIP protein, β-catenin, and proteasomes in heart function. Our results might also bring new information concerning the intracellular processes and signal pathways involved in the regulation of cardiomyocytes functioning in hypertension state. In addition to cognitive significance, the results of presented studies may contribute to further successes in preventing and treatment of cardiac complications associated with hypertension.
Keywords: Calcyclin-binding protein/Siah-1-interacting protein; LMP7; heart; hypertension; immunohistochemistry; β-Catenin.