BACKGROUND:Ezetimibe is an inhibitor of cholesterol absorption in the intestine. We examined whether ezetimibe improves endothelial function, and if so, what mechanisms are involved. METHODS AND RESULTS:Nineteen healthy subjects (male/female 14/5; mean age, 31±3 [SD] years-old) were randomized to receive ezetimibe (10mg/day) or pravastatin (10mg/day) for 4 weeks in a cross-over manner with a 4-week washout interval. Lipid profiles, flow-mediated dilatation (FMD) and Rho-kinase activity of circulating leukocytes (the extent of phosphorylation of myosin binding subunit, a Rho-kinase substrate) were examined. We also evaluated remnant-like particle cholesterol (RLP-C) known as an up-regulator of Rho-kinase and cholesterol absorption status by measuring cholestanol and campesterol/lathosterol ratio (CLR) (both absorption markers). Although ezetimibe and pravastatin equally reduced low-density lipoprotein cholesterol (E: -25% vs. P: -21%), the CLR was reduced by ezetimibe but was rather increased by pravastatin (E: -41% vs. P: +37%; P<0.01). Reduction in RLP-C by ezetimibe was greater compared with pravastatin (E: -33% vs. P: -14%; P<0.05). Importantly, ezetimibe significantly improved FMD (26%, P<0.05) and reduced Rho-kinase activity (-21%, P<0.05), whereas pravastatin had no such effects. A significant correlation was noted between the reduction in cholestanol and the improvement in FMD (P<0.05). CONCLUSIONS: These results indicate that ezetimibe improves endothelial function and inhibits Rho-kinase activity associated with the inhibition of cholesterol absorption, suggesting novel anti-atherogenic effects of the agent in humans.
RCT Entities:
BACKGROUND:Ezetimibe is an inhibitor of cholesterol absorption in the intestine. We examined whether ezetimibe improves endothelial function, and if so, what mechanisms are involved. METHODS AND RESULTS: Nineteen healthy subjects (male/female 14/5; mean age, 31±3 [SD] years-old) were randomized to receive ezetimibe (10mg/day) or pravastatin (10mg/day) for 4 weeks in a cross-over manner with a 4-week washout interval. Lipid profiles, flow-mediated dilatation (FMD) and Rho-kinase activity of circulating leukocytes (the extent of phosphorylation of myosin binding subunit, a Rho-kinase substrate) were examined. We also evaluated remnant-like particle cholesterol (RLP-C) known as an up-regulator of Rho-kinase and cholesterol absorption status by measuring cholestanol and campesterol/lathosterol ratio (CLR) (both absorption markers). Although ezetimibe and pravastatin equally reduced low-density lipoprotein cholesterol (E: -25% vs. P: -21%), the CLR was reduced by ezetimibe but was rather increased by pravastatin (E: -41% vs. P: +37%; P<0.01). Reduction in RLP-C by ezetimibe was greater compared with pravastatin (E: -33% vs. P: -14%; P<0.05). Importantly, ezetimibe significantly improved FMD (26%, P<0.05) and reduced Rho-kinase activity (-21%, P<0.05), whereas pravastatin had no such effects. A significant correlation was noted between the reduction in cholestanol and the improvement in FMD (P<0.05). CONCLUSIONS: These results indicate that ezetimibe improves endothelial function and inhibits Rho-kinase activity associated with the inhibition of cholesterol absorption, suggesting novel anti-atherogenic effects of the agent in humans.
Authors: Andrei C Sposito; Ikaro Breder; Joaquim Barreto; Jessica Breder; Isabella Bonilha; Marcus Lima; Alessandra Oliveira; Vaneza Wolf; Beatriz Luchiari; Helison R do Carmo; Daniel Munhoz; Daniela Oliveira; Otavio R Coelho-Filho; Otavio R Coelho; Jose Roberto Matos-Souza; Filipe A Moura; Luiz Sergio F de Carvalho; Wilson Nadruz; Thiago Quinaglia; Sheila T Kimura-Medorima Journal: Cardiovasc Diabetol Date: 2022-08-06 Impact factor: 8.949