CARFMAP: A Curated Pathway Map of Cardiac Fibroblasts

Abstract

The adult mammalian heart contains multiple cell types that work in unison under tightly regulated conditions to maintain homeostasis. Cardiac fibroblasts are a significant and unique population of non-muscle cells in the heart that have recently gained substantial interest in the cardiac biology community. To better understand this renaissance cell, it is essential to systematically survey what has been known in the literature about the cellular and molecular processes involved. We have built CARFMAP (http://visionet.erc.monash.edu.au/CARFMAP), an interactive cardiac fibroblast pathway map derived from the biomedical literature using a software-assisted manual data collection approach. CARFMAP is an information-rich interactive tool that enables cardiac biologists to explore the large body of literature in various creative ways. There is surprisingly little overlap between the cardiac fibroblast pathway map, a foreskin fibroblast pathway map, and a whole mouse organism signalling pathway map from the REACTOME database. Among the use cases of CARFMAP is a common task in our cardiac biology laboratory of identifying new genes that are (1) relevant to cardiac literature, and (2) differentially regulated in high-throughput assays. From the expression profiles of mouse cardiac and tail fibroblasts, we employed CARFMAP to characterise cardiac fibroblast pathways. Using CARFMAP in conjunction with transcriptomic data, we generated a stringent list of six genes that would not have been singled out using bioinformatics analyses alone. Experimental validation showed that five genes (Mmp3, Il6, Edn1, Pdgfc and Fgf10) are differentially regulated in the cardiac fibroblast. CARFMAP is a powerful tool for systems analyses of cardiac fibroblasts, facilitating systems-level cardiovascular research.

Inhibition of CXCR4 inhibits the proliferation and osteogenic potential of fibroblasts from ankylosing spondylitis via the Wnt/β‑catenin pathway

“…There was a loose correlation between CD90 expression and cuboidal morphology of non-activated cells (20). An additional commonly used cell marker for fibroblasts is vimentin, which has a high level of sensitivity for fibroblast labelling (32). Vimentin was originally used as an endothelial cell marker.…”

Cardiac Fibroblast Activation Post-Myocardial Infarction: Current Knowledge Gaps

“…Nim and colleagues have recently built a very extensive curated pathway map of cardiac fibroblasts (CARFMAP; http://visionet.erc.monash.edu.au/CARFMAP), an interactive map stemming from the current biomedical literature and utilizing a software-assisted manual data collection approach [77]. The CARFMAP allows users to explore the large body of fibroblast literature in various interactive ways.…”

“…The CARFMAP allows users to explore the large body of fibroblast literature in various interactive ways. From expression profiles of mouse cardiac and tail fibroblasts, the authors have applied CARFMAP to characterize cardiac fibroblast pathways [77]. Building on this infrastructure to include details of post-MI fibroblast activation will provide a highly useful resource.…”

Multiscale Coupling of an Agent-Based Model of Tissue Fibrosis and a Logic-Based Model of Intracellular Signaling

“…This inherent complexity of the biological phenomenon necessitates the development of computational models to design and test therapeutic interventions that potentially have opposite effects at different phases throughout the wound healing cascade. Previous computational models have extensively characterized cardiac fibroblast signaling pathways and expression profiles to provide information about fibroblast activation and kinetics (Nim et al, 2015;Zeigler et al, 2016a,b), but fibroblast activation has generally been studied in response to single stimuli in vitro. Other researchers in the field have noted the need to understand fibroblast activation in response to mixed stimuli, and have called for the development of computational models that can integrate the effects of spatial and temporal shifts in fibroblast activation, with the cell-cell interactions and cell-matrix interactions that coordinate the short and long-term remodeling of scar tissue (Ma et al, 2017).…”