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| Item Type: | Preprint |
|---|---|
| Title: | Cytokines as potential novel therapeutic targets in severe inflammatory cardiomyopathy |
| Creators Name: | Suwalski, P., Golpour, A., Weiner, J., Musigk, N., Balzer, F., Giesa, N., Amr, A., Trebing, J., Sedaghat, F., Meder, B., Beule, D., 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. |
| Source: | bioRxiv |
| 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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