Introduction: Cardiovascular disorders such as heart failure, account for a significant proportion of morbidity and mortality across the globe. The mechanism driving heart failure is complex and can arise from several different pathological events, including a myocardial infarction; ultimately resulting in excessive fibrosis of the heart and a substantial reduction in cardiac compliance. Elevation in inflammatory mediators such as cortisol and TGF-β1 have been implicated in the progression of heart failure, and their interactions with one of the primary cell types of the heart, the cardiac fibroblast, has been linked to an increase in cardiac fibrosis. The cardiac fibroblast, while it plays a substantial role in wound repair and fibrosis, its activity is upregulated under stress when it is transformed to a myofibroblast phenotype. While TGF-β1 signalling on cardiac fibroblast and its effect on transforming cardiac fibroblasts to myofibroblasts is well defined the role of cortisol in heart failure and specifically on fibroblast function has not been studied. Nor has any interactions between the two compounds been explored in an in vitro model. Experimental Aims: This study aimed to evaluate the effects of the stress and inflammatory mediators, cortisol and TGF-β1, on cell metabolic activity and cytotoxicity measured using an MTT, CCK-8, LDH assays and an object count via plate reader. The RNA expression of fibrosis genes and protein expression of α-smooth muscle actin (α-SMA) and the glucocorticoid receptor (GR) was also measured, using NanoString nCounter analysis and western blot respectively. All of these experiments were completed using primary human cardiac fibroblasts, with the purpose of determining the interaction between stress and inflammatory mediators on cardiac fibroblast function to establish a possible contributor to the pathology of heart failure. [...]