Suppression of IL-1β promotes beneficial accumulation of fibroblast-like cells in atherosclerotic plaques in clonal hematopoiesis Journal Article
| Authors: | Fidler, T. P.; Dunbar, A.; Kim, E.; Hardaway, B.; Pauli, J.; Xue, C.; Abramowicz, S.; Xiao, T.; O'Connor, K.; Sachs, N.; Wang, N.; Maegdefessel, L.; Levine, R.; Reilly, M.; Tall, A. R. |
| Article Title: | Suppression of IL-1β promotes beneficial accumulation of fibroblast-like cells in atherosclerotic plaques in clonal hematopoiesis |
| Abstract: | Clonal hematopoiesis (CH) is an independent risk factor for atherosclerotic cardiovascular disease. Murine models of CH suggest a central role of inflammasomes and IL-1β in accelerated atherosclerosis and plaque destabilization. Here we show using single-cell RNA sequencing in human carotid plaques that inflammasome components are enriched in macrophages, while the receptor for IL-1β is enriched in fibroblasts and smooth muscle cells (SMCs). To address the role of inflammatory crosstalk in features of plaque destabilization, we conducted SMC fate mapping in Ldlr −/− mice modeling Jak2 VF or Tet2 CH treated with IL-1β antibodies. Unexpectedly, this treatment minimally affected SMC differentiation, leading instead to a prominent expansion of fibroblast-like cells. Depletion of fibroblasts from mice treated with IL-1β antibody resulted in thinner fibrous caps. Conversely, genetic inactivation of Jak2 VF during plaque regression promoted fibroblast accumulation and fibrous cap thickening. Our studies suggest that suppression of inflammasomes promotes plaque stabilization by recruiting fibroblast-like cells to the fibrous cap. © 2024, The Author(s), under exclusive licence to Springer Nature Limited. |
| Journal Title: | Nature Cardiovascular Research |
| Volume: | 3 |
| Issue: | 1 |
| ISSN: | 2731-0590 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2024-01-01 |
| Start Page: | 60 |
| End Page: | 75 |
| Language: | English |
| DOI: | 10.1038/s44161-023-00405-9 |
| PROVIDER: | scopus |
| PMCID: | PMC10868728 |
| PUBMED: | 38362011 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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