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| Item Type: | Article |
|---|---|
| Title: | Multiomic analyses uncover immunological signatures in acute and chronic coronary syndromes |
| Creators Name: | Pekayvaz, K. and Losert, C. and Knottenberg, V. and Gold, C. and van Blokland, I.V. and Oelen, R. and Groot, H.E. and Benjamins, J.W. and Brambs, S. and Kaiser, R. and Gottschlich, A. and Hoffmann, G.V. and Eivers, L. and Martinez-Navarro, A. and Bruns, N. and Stiller, S. and Akgöl, S. and Yue, K. and Polewka, V. and Escaig, R. and Joppich, M. and Janjic, A. and Popp, O. and Kobold, S. and Petzold, T. and Zimmer, R. and Enard, W. and Saar, K. and Mertins, P. and Huebner, N. and van der Harst, P. and Franke, L.H. and van der Wijst, M.G.P. and Massberg, S. and Heinig, M. and Nicolai, L. and Stark, K. |
| Abstract: | Acute and chronic coronary syndromes (ACS and CCS) are leading causes of mortality. Inflammation is considered a key pathogenic driver of these diseases, but the underlying immune states and their clinical implications remain poorly understood. Multiomic factor analysis (MOFA) allows unsupervised data exploration across multiple data types, identifying major axes of variation and associating these with underlying molecular processes. We hypothesized that applying MOFA to multiomic data obtained from blood might uncover hidden sources of variance and provide pathophysiological insights linked to clinical needs. Here we compile a longitudinal multiomic dataset of the systemic immune landscape in both ACS and CCS (n = 62 patients in total, n = 15 women and n = 47 men) and validate this in an external cohort (n = 55 patients in total, n = 11 women and n = 44 men). MOFA reveals multicellular immune signatures characterized by distinct monocyte, natural killer and T cell substates and immune-communication pathways that explain a large proportion of inter-patient variance. We also identify specific factors that reflect disease state or associate with treatment outcome in ACS as measured using left ventricular ejection fraction. Hence, this study provides proof-of-concept evidence for the ability of MOFA to uncover multicellular immune programs in cardiovascular disease, opening new directions for mechanistic, biomarker and therapeutic studies. |
| Keywords: | Acute Coronary Syndrome, Chronic Disease, Inflammation, Natural Killer Cells, Monocytes, T-Lymphocytes / Immunology |
| Source: | Nature Medicine |
| ISSN: | 1078-8956 |
| Publisher: | Nature Publishing Group |
| Date: | 2024 |
| Official Publication: | https://doi.org/10.1038/s41591-024-02953-4 |
| PubMed: | View item in PubMed |
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