| First Author | Fidler TP | Year | 2024 |
| Journal | Nat Cardiovasc Res | Volume | 3 |
| Issue | 1 | Pages | 60-75 |
| PubMed ID | 38362011 | Mgi Jnum | J:354893 |
| Mgi Id | MGI:7736805 | Doi | 10.1038/s44161-023-00405-9 |
| Citation | Fidler TP, et al. (2024) Suppression of IL-1beta promotes beneficial accumulation of fibroblast-like cells in atherosclerotic plaques in clonal hematopoiesis. Nat Cardiovasc Res 3(1):60-75 |
| abstractText | Clonal hematopoiesis (CH) is an independent risk factor for atherosclerotic cardiovascular disease. Murine models of CH suggest a central role of inflammasomes and IL-1beta 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-1beta 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-1beta 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-1beta 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. |
