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

Cardiovascular Diabetology

Original Investigation

Jia-Shiong Chen¹  Shing-Jong Lin²  Hsin-Bang Leu³  Po-Hsun Huang⁴  Tao-Cheng Wu⁴  Ting-Ting Chang⁵  Jaw-Wen Chen⁶  Liang-Yu Lin⁷  Chin-Chou Huang⁸ 

[1] Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan;Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan;Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan;Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan;Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan;Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan;Department of Medicine, Healthcare and Management Center, Taipei Veterans General Hospital, Taipei, Taiwan;Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan;Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan;Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan;Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan;Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan;Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan;Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan;Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan;Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan;Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan;Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan;Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan;Department of Education, Taipei Veterans General Hospital, Taipei, Taiwan;

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

DOI  :  10.1186/s12933-014-0111-1

 received in 2014-04-26, accepted in 2014-07-07,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundCirculating 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.MethodsA 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.ResultsA 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.ConclusionsWhile 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 registrationThis trial is registered at ClinicalTrials.gov, NCT01386853.

【 授权许可】

Unknown   
© Lin et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.