©© 2009 American College of Clinical Pharmacology, Inc.
The Journal of Clinical Pharmacology, 10.1177/0091270009340889
Pleiotropic Effects of Atorvastatin on Monocytes in Atherosclerotic Patients
Zhi-hao Wang 1,
Xiao-lin Liu 2,
Ming Zhong 1,
Li-ping Zhang 3,
Yuan-yuan Shang 1,
Xiao-yan Hu 3,
Li Li 1,
Yun Zhang 1,
Jing-ti Deng 3,
and
Wei Zhang 1*
1 Hospital of Shandong University
2 Affiliated Hospital of Binzhou Medical College
3 Medical School of Shandong University
* To whom correspondence should be addressed. E-mail: zhangweisdu{at}gmail.com.
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Abstract |
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The objective of this study was to investigate the gene expression signature of monocyte/macrophages and the pleiotropic effects of atorvastatin on monocytes in atherosclerotic patients. Forty patients with coronary heart diseases were randomly assigned to double-blind therapy with either 20 or 80 mg per day of atorvastatin. Follow-up visits occurred at weeks 6 and 12, including complete chemistry and lipid analyses and quantification of 14 target genes in monocytes. After 12 weeks of therapy, both groups gained beneficial alterations in lipid profiles. Both groups experienced significant reductions in gene expression of lipoprotein-associated phospholipase A2, CD13, leptin receptor, matrix metalloproteases-1, legumain, and prolyl oligopeptidase after 12 weeks of therapy. Only tumor protein 53 was increased in the atorvastatin 80-mg group. Moreover, nonsignificant interactions between dosage and duration of therapy were found. The pleiotropic effects of statins in atherosclerotic patients include increased expression of genes involved in apoptosis of monocyte/ macrophage, inhibition of inflammatory responses, antioxidant properties, prevention of foam cell formation, and stabilization of atherosclerotic plaques. This property fuels potential clinical significance.