Monocytes Increase Human Cardiac Myofibroblast-Mediated Extracellular Matrix Remodeling Through TGF-β1

American Journal of Physiology. Heart and Circulatory Physiology
Holly E M MewhortPaul W M Fedak

Abstract

Following myocardial infarction (MI), cardiac myofibroblasts remodel the extracellular matrix (ECM) preventing mechanical complications. However, prolonged myofibroblast activity leads to dysregulation of the ECM, maladaptive remodeling, fibrosis and heart failure (HF). Chronic inflammation is believed to drive persistent myofibroblast activity, however, the mechanisms are unclear. We assessed the influence of peripheral blood monocytes on human cardiac myofibroblast activity in a 3D ECM microenvironment. Human cardiac myofibroblasts isolated from surgical biopsies of the right atrium and left ventricle were seeded into 3D collagen matrices. Peripheral blood monocytes were isolated from healthy human donors and co-cultured with myofibroblasts. Monocytes increased myofibroblast activity measured by collagen gel contraction (baseline: 57.6±5.9% vs. co-culture: 65.2±7.1% contraction; p<0.01) and increased local ECM remodeling quantified by confocal microscopy. Under co-culture conditions that allow indirect cellular interaction via paracrine factors but prevent direct cell-cell contact, monocytes had minimal effects on myofibroblast activity (17.9±11.1% vs. 6.4±7.0% increase, respectively; p<0.01). When cells were cultured under d...Continue Reading

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