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Cytokines as potential novel therapeutic targets in severe inflammatory cardiomyopathy

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Title:Cytokines as potential novel therapeutic targets in severe inflammatory cardiomyopathy
Creators Name:Suwalski, P. and Golpour, A. and Weiner, J. and Musigk, N. and Balzer, F. and Giesa, N. and Amr, A. and Trebing, J. and Sedaghat, F. and Meder, B. and Beule, D. and Landmesser, U. and Heidecker, B.
Abstract:BACKGROUND: Despite currently available state-of-the art therapies, a substantial proportion of patients with inflammatory cardiomyopathy progresses to advanced heart failure. There is an urgent need for novel therapies to improve outcomes. We hypothesized that elevated cyto-kine levels in inflammatory cardiomyopathy may lead to cardiac injury and that specific cyto-kines are associated with severely decreased left ventricular function consequently, thereby suggesting their potential as therapeutic targets. METHODS AND RESULTS: Blood samples collected from 529 patients at 2 registries were inves-tigated. First, in a derivation cohort of inflammatory cardiomyopathy from our medical center (n=63), we discovered cytokines that correlate inversely with severely decreased left ventricu-lar ejection fraction (LVEF). We confirmed reproducibility of our results in an independent cohort from a national registry (n=425) and to some degree generalizability in a small cohort of idiopathic dilated cardiomyopathy (IDCM, n=41). In total, we identified 82 cytokines asso-ciated with severely decreased LVEF (FDR < 0.05); a small portion had been previously pro-posed as therapeutic targets, while others emerged as novel discoveries. Finally, real-world data from electronic medical records further indicated the potential of inhibitors targeting cy-tokines of interest to confer a cardioprotective effect. CONCLUSIONS: We identified 82 cytokines associated with severe inflammatory cardiomyopa-thy. Our data were highly significant, reproducible, and generalizable to IDCM. The fact that some of the cytokines had been suggested as potential targets in prior literature supports va-lidity and plausibility of our data. Given that inhibition of cytokines is technically feasible, the identified proteins are compelling potential novel therapeutic targets.
Publisher:Cold Spring Harbor Laboratory Press
Article Number:2023.07.27.23293253
Date:4 August 2023
Official Publication:https://doi.org/10.1101/2023.07.27.23293253

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