Human Cardiac Fibroblasts Isolated from Patients with Severe Heart Failure Are Immune-competent Cells Mediating an Inflammatory Response

This study was aimed to elucidate the immunoregulatory properties of human cardiac fibroblasts cultured under pro-inflammatory and hypoxic conditions. Human heart tissue for isolating cardiac cells is generally hard to obtain, particularly from all four chambers of the same heart. Since different parts of the heart have different functions and therefore may have different immunoregulatory properties, ability to analyse cells from all chambers allows for a unique and comprehensive investigation. Cells were isolated from all four chambers of the heart from patients undergoing cardiac transplantation surgery due to severe chronic heart failure (CHF) (n = 6). Cells isolated from one donor heart, were used for comparison with the experimental group. Primary cultured human cardiac fibroblasts were treated with Lipopolysaccharide (LPS) to induce an inflammatory response. Cells were also subjected to hypoxia. To determine immunoregulatory properties of the cells, cytokine and chemokine profiles were determined using multiplex ELISA. RESULTS: On average, the fibroblasts population constituted approximately 90% of the expanded non-myocytes. Levels of cytokines and chemokines were markedly increased in human cardiac fibroblasts cultured under inflammatory conditions, with a similar response in fibroblasts from all compartments of the heart. Unexpectedly, hypoxia did not further augment cytokine and chemokine secretion. In conclusion, human cardiac fibroblasts are a robust source of pro-inflammatory mediators in the failing heart, independent of hypoxia, and might play a critical role in inflammation associated with the pathogenesis of CHF.