Periodic Reporting for period 2 - CaReSyAn (Combatting the CardioRenal Syndrome: towards an integrative Analysis to reduce cardiovascular burden in chronic kidney disease)
Reporting period: 2020-01-01 to 2021-12-31
As one highlight, novel calcification-regulatory peptides were identified by our partners as candidates for novel therapeutic strategies targeting increased cardiovascular calcification in patients with chronic kidney disease, resulting in a European patent application. Furthermore, building on the successful collaborations in CaReSyAn, a new joint institute between the RWTH Aachen and the Maastricht University was created, named the Aachen-Maastricht Institute for CardioRenal Disease (AMICARE), to ensure continuation of European training and research efforts as in CaReSyAn also beyond the borders of this consortium.
On research level, we identified biomarkers of the cardiorenal syndrome by proteomics/peptidomics analysis of patient biomaterial. This includes the identification of diagnostic biomarkers for diagnosis of increased cardiovascular risk in patients with chronic kidney disease. Furthermore, we identified and characterized biomarkers for vascular calcification in patients with chronic kidney disease, with vascular calcification highly contributing to cardiovascular morbidity in these patients. Based on these findings, high-dimensional network models of the cardiorenal syndrome were generated using bioinformatics, with the aim to provide deeper insights into the value of biomarker candidates in diagnostic and predictive signatures of the disease. Also, we studied in detail the underlying pathological processes of the cardiorenal syndrome, since such insights are required to trigger the development of novel therapeutic strategies specifically tailored to the cardiorenal patient. For example, we studied how vascular calcification is affected by the novel biomarkers or by so-called post-translational modifications of proteins that we identified to be deregulated in the cardiorenal syndrome. An additional focus was set on how vascular calcification is influenced by uremic toxins, which are substances that are highly accumulating patients with a failing kidney function. Moreover, our studies revealed novel insights into premature aging of the cardiovascular system as well as on the vulnerability of cardiomyocytes in the context of chronic kidney disease. Finally, we proceeded also to testing the potential effect of novel therapeutic strategies in reducing pathological mechanisms linked to the cardiorenal syndrome in preclinical studies. As a highlight, a novel calcification-blocking peptide was discovered and fully characterized in terms of protective effects towards vascular calcification. Also, a potential therapy interfering with one of the identified biomarkers of the cardiorenal syndrome revealed to provide protection against vascular calcification in preclinical studies. Overall, we can summarize that training as well as research within CaReSyAn covered all aspects from discovery of novel disease regulators up to deep characterization of disease mechanisms and the initiation of therapeutic translation strategies.