Pericardial Fluid of Patients with Coronary Artery Disease Can Drive Fibrosis via TGF-Beta Signalling Pathway

Pericardial fluid (PF) helps maintain homeostatic conditions that facilitate optimal heart function. We have yet to understand how cardiovascular pathologies affect the profile of PF. We hypothesized that human PF contains immune markers that can be affected by different pathologies and contribute to inflammatory-mediated processes, such as fibrosis. PF was collected from patients undergoing cardiac surgery. Multiplex analysis was performed to determine the composition of inflammatory markers and soluble mediators. A gel contraction assay was used to investigate the fibrotic potential of PF. RNA-sequencing was used to elucidate the mechanisms driving the pro-fibrotic properties of PF. With the results of these multiple approaches we show that the acellular component of PF has pro-fibrotic characteristics and suggest putative mechanisms that can explain such observations. Overall design: Patients undergoing isolated CABG and valvular surgeries at Foothills Medical Centre (Calgary, Canada) were prospectively enrolled in the study after providing written informed consent. Native Pericardial Fluid (PF) was obtained from all patients before the institution of cardiopulmonary bypass (CPB) and the administration of heparin or steroids. Pericardial tissue and right atrial appendage were also collected from patients. Human cardiac fibroblasts were isolated from right atrial appendage taken from consenting patients, then culture alone, with pericardial fluid supernatant, or with the supernatant plus TGF-ß1 receptor inhibitor (TGF-ßR1i).