Vascular protective effects of ezetimibe in ApoE-deficient mice

Inhibition of intestinal cholesterol absorption decreases atherosclerosis but not adipose tissue inflammation

“…Although the dramatic effect of ezetimibe on triglyceride levels due to a reduction in levels of VLDL/IDL has not been reported in human subjects receiving ezetimibe treatment, a few small clinical studies have evaluated effects of ezetimibe on the extent of atherosclerotic lesions, especially as lesion size showed a strongly positive correlation with plasma triglyceride levels. Ezetimibe has previously been shown to reduce atherosclerosis in apoE-defi cient mice, in which it also led to a marked reduction of VLDL/IDLlike particles ( 11,29 ), which are the main lipoproteins that accumulate in that mouse model. HDL also increased in the apoE-defi cient mice with ezetimibe treatment ( 11,29 ), an effect that was not observed in the Ldlr Ϫ / Ϫ mice in our study.…”

Ezetimibe Monotherapy Ameliorates Vascular Function in Patients with Hypercholesterolemia Through Decreasing Oxidative Stress

“…Yagi et al have already reported that ezetimibe ameliorates insulin resistance, the degree of inflammation and oxidative stress 6) . In addition, Nakagami et al reported that ezetimibe treatment prevented the progression of atherosclerosis by suppressing oxidative stress in mice lacking apolipoprotein E 15) . Since it has been reported that oxidative stress was involved in hypertension or renal dysfunction in conditions with an activated renin-angiotensin system 16,17) , attenuation of oxidative stress by pharmacological manipulation is thought to be a valid therapeutic approach for preventing cardiovascular diseases.…”

Dietary Cholesterol Oxidation Products Accelerate Plaque Destabilization and Rupture Associated with Monocyte Infiltration/Activation via the MCP-1-CCR2 Pathway in Mouse Brachiocephalic Arteries: Therapeutic Effects of Ezetimibe

“…(3) oxysterol HFD-vehicle group (4) oxysterol HFD treated with ezetimibe group. The dose of ezetimibe used in this study was selected because of the effectiveness reported in prior studies 14,15) . Systolic blood pressure and heart rate were measured by the tail-cuff method before and 4 weeks after angiotensin Ⅱ infusion.…”

“…Ezetimibe, an inhibitor of the cholesterol transporter Niemann-Pick C1 Like 1 (NPC1L1) protein 12) , inhibits the absorption of both dietary cholesterol and oxysterols in animals and humans 13) , and thereby the development of aortic atherosclerosis induced by a regular Western diet containing pure cholesterol in animals 14,15) . Prior studies, however, have not addressed the therapeutic effects of ezetimibe on atherosclerotic plaque development, destabilization and rupture induced by dietary oxysterols.…”