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Open Access Original investigation

Effects of pitavastatin versus atorvastatin on the peripheral endothelial progenitor cells and vascular endothelial growth factor in high-risk patients: a pilot prospective, double-blind, randomized study

Liang-Yu Lin123, Chin-Chou Huang134, Jia-Shiong Chen5, Tao-Cheng Wu356, Hsin-Bang Leu357, Po-Hsun Huang356, Ting-Ting Chang1, Shing-Jong Lin689 and Jaw-Wen Chen169*

Author Affiliations

1 Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan

2 Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

3 Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan

4 Department of Education, Taipei Veterans General Hospital, Taipei, Taiwan

5 Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan

6 Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

7 Department of Medicine, Healthcare and Management Center, Taipei Veterans General Hospital, Taipei, Taiwan

8 Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan

9 Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan

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Cardiovascular Diabetology 2014, 13:111  doi:10.1186/s12933-014-0111-1

Published: 16 July 2014

Abstract

Background

Circulating endothelial progenitor cells (EPCs) reflect endothelial repair capacity and may be a significant marker for the clinical outcomes of cardiovascular disease. While some high-dose statin treatments may improve endothelial function, it is not known whether different statins may have similar effects on EPCs.This study aimed to investigate the potential class effects of different statin treatment including pitavastatin and atorvastatin on circulating EPCs in clinical setting.

Methods

A pilot prospective, double-blind, randomized study was conducted to evaluate the ordinary dose of pitavastatin (2 mg daily) or atorvastatin (10 mg daily) treatment for 12 weeks on circulating EPCs in patients with cardiovascular risk such as hypercholesterolemia and type 2 diabetes mellitus (T2DM). Additional in vitro study was conducted to clarify the direct effects of both statins on EPCs from the patients.

Results

A total of 26 patients (19 with T2DM) completed the study. While the lipid-lowering effects were similar in both treatments, the counts of circulating CD34+KDR+EPCs were significantly increased (from 0.021 ± 0.015 to 0.054 ± 0.044% of gated mononuclear cells, P < 0.05) only by pitavastatin treatment. Besides, plasma asymmetric dimethylarginine level was reduced (from 0.68 ± 0.10 to 0.53 ± 0.12 μmol/L, P < 0.05) by atorvastatin, and plasma vascular endothelial growth factor (VEGF) level was increased (from 74.33 ± 32.26 to 98.65 ± 46.64 pg/mL, P < 0.05) by pitavastatin. In the in vitro study, while both statins increased endothelial nitric oxide synthase (eNOS) expression, only pitavastatin increased the phosphorylation of eNOS in EPCs. Pitavastatin but not atorvastatin ameliorated the adhesion ability of early EPCs and the migration and tube formation capacities of late EPCs.

Conclusions

While both statins similarly reduced plasma lipids, only pitavastatin increased plasma VEGF level and circulating EPCs in high-risk patients, which is probably related to the differential pleiotropic effects of different statins.

Trial registration

This trial is registered at ClinicalTrials.gov, NCT01386853 webcite.

Keywords:
Pitavastatin; Atorvastatin; Hypercholesterolemia; Endothelial progenitor cell; Endothelial nitric oxide synthase; Vascular endothelial growth factor