Key result
Extracellular matrix sub-types and mechanical cyclical stretch differentially affected the expression of pro-fibrotic genes and the response to TGFβ1 in primary human cardiac fibroblast cells.
The specific extracellular matrix microenvironment and mechanical stretch significantly modulate the pro-fibrotic response of human cardiac fibroblasts to TGFβ1, providing insight into myocardial fibrosis pathophysiology.
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No immediate clinical implications; leaves open whether ECM-specific or stretch-targeted interventions will reduce cardiac fibrosis in patients.
Understanding the impact of extracellular matrix sub-types and mechanical stretch on cardiac fibroblast activity is required to help unravel the pathophysiology of myocardial fibrotic diseases. Therefore, the purpose of this study was to investigate pro-fibrotic responses of primary human cardiac fibroblast cells exposed to different extracellular matrix components, including collagen sub-types I, III, IV, VI and laminin. The impact of mechanical cyclical stretch and treatment with transforming growth factor beta 1 (TGFβ1) on collagen 1, collagen 3 and alpha smooth muscle actin mRNA expression on different matrices was assessed using quantitative real-time PCR. Our results revealed that all of the matrices studied not only affected the expression of pro-fibrotic genes in primary human cardiac fibroblast cells at rest but also affected their response to TGFβ1. In addition, differential cellular responses to mechanical cyclical stretch were observed depending on the type of matrix the cells were adhered to. These findings may give insight into the impact of selective pathological deposition of extracellular matrix proteins within different disease states and how these could impact the fibrotic environment.
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Watson et al. (2014) studied Myocardial fibrotic diseases. Extracellular matrix components, mechanical cyclical stretch, and TGFβ1 vs. Different matrices and resting conditions was evaluated on Expression of pro-fibrotic genes (collagen 1, collagen 3, and alpha smooth muscle actin mRNA). Extracellular matrix sub-types and mechanical cyclical stretch differentially affected the expression of pro-fibrotic genes and the response to TGFβ1 in primary human cardiac fibroblast cells.
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