Effects of ezetimibe on endothelial progenitor cells and microparticles in high-risk patients.
Imbalance on endothelial turnover can predict cardiovascular outcomes. We aimed at evaluating the effects of lipid-modifying therapies on circulating endothelial progenitor cells (EPCs), endothelial microparticles (EMPs), and platelet microparticles (PMPs) in high cardiovascular risk subjects with elevated C-reactive protein (CRP). Sixty-three individuals with coronary heart disease (CHD) or CHD risk equivalent on stable statin therapy, with LDL-cholesterol <100 mg/dL and CRP ≥ 2.0 mg/L were selected. After a 4-week run-in period with atorvastatin 10 mg, those with persistent CRP ≥ 2.0 mg/L were randomized to another 4-week treatment period with atorvastatin 40 mg, ezetimibe 10 mg or atorvastatin 40 mg/ezetimibe 10 mg. EPC (CD34(+)/CD133(+)/KDR(+)), EMP (CD51(+)), and PMP (CD42(+)/CD31(+)) were quantified by flow cytometry. Atorvastatin 40 mg and atorvastatin 40 mg/ezetimibe 10 mg reduced LDL-cholesterol (P < 0.001, paired T test, vs. baseline). Combined therapy, but not ezetimibe reduced CRP. CD34(+)/KDR(+) EPC were reduced after ezetimibe alone (P = 0.011 vs. baseline, Wilcoxon test) or combined with atorvastatin (P = 0.016 vs. baseline, Wilcoxon test). In addition, ezetimibe increased CD51(+) EMP (P = 0.017 vs. baseline, Wilcoxon test). No correlations between these markers and LDL-cholesterol or CRP were observed. These results contribute to understand the link between inflammation and vascular homeostasis and highlight the broader benefit of statins decreasing inflammation and preventing microparticles release, an effect not observed with ezetimibe alone.
Lipids, Atherosclerosis and Vascular Biology Section, Cardiology Division, Department of Medicine, Federal University of Sao Paulo, Rua Pedro de Toledo, 276, São Paulo, SP, 04039030, Brazil.
Lívia Campos Amaral
LC
Lins
Carolina Nunes
CN
França
Francisco Antonio Helfenstein
FA
Fonseca
Simone Pinto Melo
SP
Barbosa
Lívia Nascimento
LN
Matos
Ana Carolina
AC
Aguirre
Henrique Tria
HT
Bianco
Jonatas Bussador
JB
do Amaral
Maria Cristina
MC
Izar
D000368:Aged; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D000069059:Atorvastatin; D001384:Azetidines / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000166:cytology; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000473:pathology; D055252:Cell-Derived Microparticles / Q000187:drug effects* / Q000378:metabolism; D008078:Cholesterol, LDL / Q000097:blood; D004347:Drug Interactions; D066026:Endothelial Progenitor Cells / Q000187:drug effects* / Q000378:metabolism; D000069438:Ezetimibe; D006538:Heptanoic Acids / Q000494:pharmacology; D006801:Humans; D008875:Middle Aged; D011758:Pyrroles / Q000494:pharmacology; D012306:Risk
D000924:Anticholesteremic Agents; D001384:Azetidines; D015415:Biomarkers; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D011758:Pyrroles; D002097:C-Reactive Protein; D000069059:Atorvastatin; D000069438:Ezetimibe