Computational model predicts paracrine and intracellular drivers of fibroblast phenotype after myocardial infarction.

ABSTRACT: The fibroblast is a key mediator of wound healing in the heart and other organs, yet how it integrates multiple time-dependent paracrine signals to control extracellular matrix synthesis has been difficult to study in vivo. Here, we extended a computational model to simulate the dynamics of fibroblast signaling and fibrosis after myocardial infarction (MI) in response to time-dependent data for nine paracrine stimuli. This computational model was validated against dynamic collagen expression and collagen area fraction data from post-infarction rat hearts. The model predicted that while many features of the fibroblast phenotype at inflammatory or maturation phases of healing could be recapitulated by single static paracrine stimuli (interleukin-1 and angiotensin-II, respectively), mimicking

SUBMITTER: Zeigler AC 

PROVIDER: S-EPMC7434705 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature