Systems biology analysis unravels complementary action of combined Rosuvastatin and Ezetimibe therapy

Transcriptomics analysis to understand both efficacy and side effects of a cholesterol lowering drug combination therapy based on biological pathways and molecular processes affected by each drug alone or in combination. We have treated ApoE*3Leiden mice, a humanized atherosclerosis model with a unique human-like response to cholesterol-lowering drugs, with RSV and EZE alone and in combination. We demonstrate that processes affected by monotherapy can be retained and enhanced by combination therapy. In addition, combination therapy also affects a number of processes which are not predictable on basis of monotherapy – at least when analysis is performed within the borders of statistical significance. Our data however provide clues for these “non-predictable” effects. Total RNA obtained from mouse liver from mice treated with High-Cholesterol (HC) diet as control (n=8) or HC+RSV (n=8) or HC+EZE (n=8) or HC+RSV+EZE (n=8).