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- W4313591397 abstract "Abstract Fibrosis is a broad pathology of excessive scarring with substantial medical implications. The fibrotic scar is produced by myofibroblasts that interact with macrophages. Fibrosis is a complex process involving thousands of factors, therefore, to better understand fibrosis and develop new therapeutic approaches, it is necessary to simplify and clarify the underlying concepts. Recently, we described a mathematical model for a macrophage-myofibroblast cell circuit, predicting two types of fibrosis - hot fibrosis with abundant macrophages and myofibroblasts, and cold fibrosis dominated by myofibroblasts alone. To test these concepts and intervention strategies in a medically relevant system, we use a widely studied in-vivo injury model for fibrosis, myocardial infarction (MI). We show that cold fibrosis is the final outcome of MI in both mice and pigs and demonstrate that fibrosis can shift toward healing in regenerative settings. MI begind with an increase of myofibroblasts and macrophages, followed by macrophage decline leading to persistent cold fibrosis (only myofibroblasts). During this process, fibroblasts, unlike macrophages, acquire distinct fate changes. Using mathematical modeling we predict that targeting of the autocrine signal for myofibroblast division could block cold fibrosis. We identify TIMP1 as an autocrine cardiac myofibroblast growth factor in-vitro . Treatment of adult mice after MI with anti-TIMP1 antibodies reduces fibrosis in-vivo . This study shows the utility of the concepts of hot and cold fibrosis and the feasibility of our circuit-to-target approach to reduce fibrosis after acute cardiac injury by inhibiting the myofibroblast autocrine loop." @default.
- W4313591397 created "2023-01-06" @default.
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- W4313591397 date "2023-01-03" @default.
- W4313591397 modified "2023-10-17" @default.
- W4313591397 title "Circuit to target approach defines an autocrine myofibroblast loop that drives cardiac fibrosis" @default.
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- W4313591397 cites W1983097616 @default.
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- W4313591397 cites W2013428526 @default.
- W4313591397 cites W2015849705 @default.
- W4313591397 cites W2036897871 @default.
- W4313591397 cites W2066885817 @default.
- W4313591397 cites W2070412924 @default.
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- W4313591397 cites W2207494192 @default.
- W4313591397 cites W2301044272 @default.
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- W4313591397 cites W2785854718 @default.
- W4313591397 cites W2800350399 @default.
- W4313591397 cites W2890044737 @default.
- W4313591397 cites W2902050841 @default.
- W4313591397 cites W2943870140 @default.
- W4313591397 cites W2946971162 @default.
- W4313591397 cites W2951891881 @default.
- W4313591397 cites W2954952794 @default.
- W4313591397 cites W2955537388 @default.
- W4313591397 cites W2971227980 @default.
- W4313591397 cites W2972517993 @default.
- W4313591397 cites W2990914781 @default.
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- W4313591397 doi "https://doi.org/10.1101/2023.01.01.522422" @default.
- W4313591397 hasPublicationYear "2023" @default.
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