The combination of hypoxia and 2% mechanical strain synergistically induced human cardiac fibroblasts to increase the release of inflammatory and pro-fibrotic cytokines and matrix metalloproteinases.
In vitro modeling reveals that the combination of hypoxia and reduced mechanical strain is required to trigger inflammatory and pro-fibrotic cytokine release from human cardiac fibroblasts.
Upon cardiac pathological conditions such as ischemia, microenvironmental changes instruct a series of cellular responses that trigger cardiac fibroblasts-mediated tissue adaptation and inflammation. A comprehensive model of how early environmental changes may induce cardiac fibroblasts (CF) pathological responses is far from being elucidated, partly due to the lack of approaches involving complex and simultaneous environmental stimulation. Here, we provide a first analysis of human primary CF behavior by means of a multi-stimulus microdevice for combined application of cyclic mechanical strain and controlled oxygen tension. Our findings elucidate differential human CFs responses to different combinations of the above stimuli. Individual stimuli cause proliferative effects (PHH3 + mitotic cells, YAP translocation, PDGF secretion) or increase collagen presence. Interestingly, only the combination of hypoxia and a simulated loss of contractility (2% strain) is able to additionally induce increased CF release of inflammatory and pro-fibrotic cytokines and matrix metalloproteinases.
Ugolini et al. (Sat,) conducted a other in Myocardial injury / Cardiac fibrosis. Combined mechanical strain and hypoxia vs. Physoxia (5% O2) and 0% strain was evaluated on Cellular responses (proliferation, collagen production, cytokine secretion). The combination of hypoxia and 2% mechanical strain synergistically induced human cardiac fibroblasts to increase the release of inflammatory and pro-fibrotic cytokines and matrix metalloproteinases.