Grönros J, Wikström J, Brandt-Eliasson U, Forsberg GB, Behrendt M, Hansson GI, Gan LM. Effects of rosuvastatin on cardiovascular morphology and function in an ApoE-knockout mouse model of atherosclerosis. Am J Physiol Heart Circ Physiol 295: H2046-H2053, 2008. First published September 12, 2008 doi:10.1152/ajpheart.00133.2008.-This study investigated the effects of rosuvastatin on plaque progression and in vivo coronary artery function in apolipoprotein E-knockout (ApoE-KO) mice, using noninvasive high-resolution ultrasound techniques. Eightweek-old male ApoE-KO mice (n ϭ 20) were fed a high-fat diet with or without rosuvastatin (10 mol ⅐ kg Ϫ1 ⅐ day Ϫ1 ) for 16 wk. When compared with control, rosuvastatin reduced total cholesterol levels (P Ͻ 0.05) and caused significant retardation of lesion progression in the brachiocephalic artery, as visualized in vivo using an ultrasound biomicroscope (P Ͻ 0.05). Histological analysis confirmed the reduction of brachiocephalic atherosclerosis and also revealed an increase in collagen content in the statin-treated group (P Ͻ 0.05). Coronary volumetric flow was measured by simultaneous recording of Doppler velocity signals and left coronary artery morphology before and during adenosine infusion. The hyperemic flow in response to adenosine was significantly greater in left coronary artery following 16 wk of rosuvastatin treatment (P Ͻ 0.001), whereas the baseline flow was similar in both groups. In conclusion, rosuvastatin reduced brachiocephalic artery atherosclerotic plaques in ApoE-KO mice. Coronary artery function assessed using recently developed in vivo ultrasoundbased protocols, also improved. apolipoprotein E-knockout mouse; ultrasound imaging; atherosclerosis; rosuvastatin THE INHIBITION OF 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase using statins has become a standard treatment regimen in patients with atherosclerosis. In addition to their cholesterol-lowering effects (11,20), statins have been shown to retard the progression of atherosclerosis (36), improve endothelial function (37, 45), reduce systemic inflammatory markers (32, 41), and reduce cardiovascular mortality and morbidity (1). Recently, the clinical regression of coronary artery atherosclerosis was reported with the use of a thirdgeneration statin (35).Despite the success of statins, cardiovascular mortality and morbidity still remain high in developed countries. When one explores new therapeutic strategies to treat atherosclerotic cardiovascular disease, it is increasingly important to demonstrate the beneficial antiatherosclerotic effects on top of the cholesterol-lowering effect of statin as well as potential pleiotrophic effects. In line with this approach, atherosclerotic animal models that can respond to currently available statin treatments are key for translational research.The effects of various statins in atherosclerotic mice are inconclusive. Differences in genetic modifications, sex, diet, as well as differences in the statins themselves, have produced different results (55). ...