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Effects of Ezetimibe on Endothelial Progenitor Cells and Microparticles in High-Risk Patients

  • Translational Biomedical Research
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Abstract

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.

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Acknowledgments

This study was supported by research Grant #2009/50052-1 from FAPESP (Foundation for Research of the State of Sao Paulo, Brazil). LCL has received research Grant from CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil).

Conflicts of interest

The authors have no conflicts of interest to disclose.

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Authors and Affiliations

  1. 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 Lins, Carolina Nunes França, Francisco Antonio Helfenstein Fonseca, Simone Pinto Melo Barbosa, Lívia Nascimento Matos, Ana Carolina Aguirre, Henrique Tria Bianco, Jonatas Bussador do Amaral & Maria Cristina Izar

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  1. Lívia Campos Amaral Lins
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  2. Carolina Nunes França
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  5. Lívia Nascimento Matos
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  9. Maria Cristina Izar
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Correspondence to Maria Cristina Izar.

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Lívia Campos Amaral Lins and Carolina Nunes França have equally contributed for this research.

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Lins, L.C.A., França, C.N., Fonseca, F.A.H. et al. Effects of Ezetimibe on Endothelial Progenitor Cells and Microparticles in High-Risk Patients. Cell Biochem Biophys 70, 687–696 (2014). https://doi.org/10.1007/s12013-014-9973-9

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  • DOI: https://doi.org/10.1007/s12013-014-9973-9

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