Expression data from mouse model of plaque regression

Atherosclerosis is the leading underlying cause of death worldwide. We reported a mouse model of atherosclerosis regression that involves transplanting an atherosclerotic aortic arch into a normolipidemic mouse. There, emigration of plaque foam cells occurred in a CCR7 (dendritic cell migration factor) dependent manner. It was obvious, though, that other pathways are likely to be involved in this process. We therefore performed microarrays on laser captured macrophages isolated from the progression and regression environments. This yielded two major findings. Firstly, genes associated with the contractile apparatus (such as actin and myosin) that are responsible for cellular movement were differentially up-regulated under regression conditions with members of the cadherin family (serves in adhesion functions) being significantly down-regulated. Secondly, the most highly up-regulated gene under regression was arginase I, a classical marker of the M2 alternative activated macrophage. Further examination revealed that regression was characterized by macrophages displaying other M2 markers such as CD163, C-lectin receptor, mannose receptor, and Fizz-1. In addition, we applied recently introduced local causal pathway discovery methods to our microarray data that revealed that genes such as vinculin and ApoCII may play a role in the pathophysiology of atherosclerosis regression. Ultimately, the insights gained from the regression model and the different modes of analyses should lead to new therapeutic targets against cardiovascular disease. We performed microarrays on laser captured macrophages isolated from aortic arch from mouse in atherosclerosis progression and regression environments (C57Bl/6, ApoE -/-). Study was performed in two batches, with three treatment groups each: progression, regression and baseline. Profiled in the Merck/Agilent 3.0