https://doi.org/10.1007/s00392-025-02625-4
1Uniklinik RWTH Aachen Institut für Molekulare Herz-Kreislaufforschung (IMCAR) Aachen, Deutschland; 2Uniklinik RWTH Aachen Med. Klinik I - Kardiologie, Angiologie und Internistische Intensivmedizin Aachen, Deutschland; 3Universitätsklinikum Würzburg Deutsches Zentrum für Herzinsuffizienz/DZHI Würzburg, Deutschland; 4Universitätsklinikum Aachen Institut für Pathologie Aachen, Deutschland
Patients with chronic kidney disease (CKD) show a highly increased cardiovascular risk. Beyond more progressed atherosclerosis and a higher risk of myocardial infarction (MI), CKD patients also suffer from a reduced survival following MI. However, the underlying mechanisms remain largely unclear. Here, we examined the impact of CKD on cardiac function and remodeling of the heart post-MI using a mouse model of adenine-induced CKD.
After myocardial infarction, CKD mice showed a stronger cardiac dysfunction compared to non-CKD controls. While no changes were observed in cardiomyocyte apoptosis, infarction size or myofibroblast content, CKD mice showed an increased infiltration and activation of inflammatory leukocytes in the heart. Also, an accumulation of pro-inflammatory stress proteins was observed, with one candidate able to directly trigger cardiomyocyte dysfunction ex vivo. Furthermore, a combination of multiplex kinome profiling and mass spectrometry revealed increased MAP kinase activity in infarcted hearts of CKD compared to non-CKD mice along with an increased phosphorylation of a transcription factor known to be linked to cardiac dysfunction. Finally, untargeted and targeted metabolomics analyses uncovered metabolic alterations that further contribute to cardiomyocyte dysfunction.
In summary, our study revealed inflammatory and metabolic alterations in the infarcted heart of CKD compared to non-CKD mice, which jointly can explain the observed increased cardiac dysfunction in CKD after infarction.