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 Lin, Chin Chou Huang, Jia Shiong Chen, Tao Cheng Wu, Hsin Bang Leu, Po Hsun Huang, Ting Ting Chang, Shing Jong Lin, Jaw Wen Chen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

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 (2mg daily) or atorvastatin (10mg daily) treatment for 12weeks 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 ± 0.12μmol/L, P < 0.05) by atorvastatin, and plasma vascular endothelial growth factor (VEGF) level was increased (from 74.33 ± 32.26 to 98.65 ± 46.64pg/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.

Original languageEnglish
Article number111
JournalCardiovascular Diabetology
Volume13
Issue number1
DOIs
StatePublished - 16 Jul 2014

Keywords

  • Atorvastatin
  • Endothelial nitric oxide synthase
  • Endothelial progenitor cell
  • Hypercholesterolemia
  • Pitavastatin
  • Vascular endothelial growth factor

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