Artemijs Vasjanovics, Lukas Weber, Simge Baydar, Marco Cremonesi, Marinos Kallikourdis, Attila Kiss, Bruno Podesser and Georgios Kararigas
Introduction
Pressure overload (PO)-induced adverse cardiac remodelling leads to myocardial hypertrophy, increased fibrosis and a reduction in cardiac function. Inflammation is expected to play an important role, but its contribution is incompletely understood. The aim of this project was to elucidate the involvement of inflammation in PO-induced cardiac dysfunction and the effects of targeted pharmacological inhibition of a chemokine receptor.
Methods
Male C57BL/6N mice (n = 32) at the age of 9-12 weeks were employed. Mice were randomly assigned to 1) undergo transverse aortic constriction (TAC) or sham operation and 2) receive a specific inhibitor against a chemokine receptor or placebo. Following 4 weeks of treatment, echocardiography was performed followed by flow cytometric assessment of the heart, the spleen and the bone marrow.
Results
The preliminary findings reveal that TAC mice had higher body weight than sham mice. Heart rate was equal among all groups. TAC induced an increase in anterior and posterior wall thickness, as well as heart-weight-to-tibia-length ratio, and a decrease in ejection fraction and stroke volume. The pharmacological inhibition led to an improvement of these parameters. Similarly, treated mice showed a reduction in pro-inflammatory T cells in the spleen. In the heart, the Treg follow a similar trend.
Conclusions
Inhibition of a chemokine receptor led to an improvement of structural and functional parameters of the heart in response to PO. Mechanistically, flow cytometry suggests a beneficial, anti-inflammatory effect. Currently, more mice are being analysed to confirm these trends and elucidate the underlying signalling mechanism.
