# The Role of Chemokines and Small Leucine-Rich Proteoglycans in Cardiac Remodeling in Immunosuppressant-Treated Male Rats

## TL;DR

This study examines how immunosuppressive drugs affect heart tissue remodeling in rats by analyzing specific proteins and their interactions.

## Contribution

The study reveals the impact of immunosuppressive regimens on cardiac chemokine and proteoglycan expression in a rat model.

## Key findings

- Chronic use of calcineurin inhibitors with mycophenolate mofetil causes abnormal heart remodeling.
- Rapamycin may reduce the negative effects of immunosuppressive therapy on the heart.
- CXCL13 and fibromodulin are significantly involved in extracellular matrix changes in treated rats.

## Abstract

Chemokines are low-molecular-weight peptides classified as cytokines with chemotactic properties. The chemokine CXCL13 and its receptor CXCR5 play a significant role in cardiac remodeling, and their expression is markedly increased in experimental models of heart failure. Increased CXCL13 activity is associated with the expression of fibromodulin, a proteoglycan that binds and cross-links collagen fibers. The stressed heart undergoes intensive remodeling, including fibrosis. In our experiment, we investigated the effect of the most commonly used triple immunosuppressive regimens on the expression of the CXCR5 receptor, the chemokine CXCL13, and fibromodulin in rat heart tissue. For this purpose, we used Western blot analysis and ELISA. The study was started on 36 rats divided into 6 groups, which received drugs for a period of 6 months. Our results suggest that the chronic use of calcineurin inhibitors in combination with mycophenolate mofetil is a significant stress factor for the heart, leading to abnormal remodeling of the extracellular matrix. The use of rapamycin may alleviate the negative effects of immunosuppressive therapy on the heart. Our results are consistent with the results of our previous studies and provide a basis for further work aimed at understanding the pathophysiology of the development of changes in the heart with individual immunosuppressive regimens.