The Effect of Prednisone on Atherogenesis as Studied in the Macrophage Foam Cell Formation Model System.

Glucocorticoids (GCs) are a class of endogenous steroid hormones produced by the adrenal glands and controlled by the hypothalamic-pituitary-adrenal axis (HPA). One of the mechanisms of their action is achieved through ligand-receptor attachment to a class of cytosolic steroid hormone receptors termed Glucocorticoid Receptors (GRs). The formed ligand-receptor complex is a transcription factor involved in gene activation of anti-inflammatory products or repression of pro-inflammatory products \[1\]. Synthetic forms of GCs are a group of anti-inflammatory and immunosuppressive medications (e.g. Prednisone) that are widely used in clinical practice to treat inflammatory diseases (e.g. Rheumatoid Arthritis, Vasculitis, Asthma). The effectiveness of this class of drugs is limited by numerous adverse effects that include, but not limited to, insulin resistance, glucose intolerance, dyslipidemia, and hypertension, all of which are well known risk factors for cardiovascular diseases (CVD) \[2,3\]. Furthermore, recent research suggest that inflammation has a key role in development of CVD and can predict prognosis \[4\]. Inflammatory cells have an important role in the development of atherosclerotic lesion in the arteries. Blood monocyte-derived macrophages are involved in this process, and they infiltrate the lesion where they take up various forms of lipids (cholesterol - rich LDL, and oxidized LDL) as well as triglycerides - rich VLDL), followed by the formation of lipid-laden foam cells, the hallmark of early atherogenesis. Inflammatory cells and molecules as well as proteolytic enzymes secreted from inflammatory cells in the atherosclerotic lesion, have a central role in destabilizing the plaque (vulnerable plaque) leading to its rupture, which, in turn, induces thrombosis, and initiating acute coronary events \[4,5\]. Based on our understanding of the involvement of inflammation in the early development of atherosclerotic lesion, and our experience with the anti-infla