Rapid response to lipids profile and leukocyte gene expression after rosuvastatin administration in Chinese healthy volunteers.
BACKGROUND
Statins are potent lipid-lowering agents widely used in medical practice. There has been growing evidence suggesting the pleiotropic effects of statins in addition to the lipid-lowering effect. However, it is still unclear how rapidly the beneficial effects of statins occur. The transcriptome of peripheral blood cells can be used as a sensor to drug therapy. The purpose of the study was to investigate the acute effects of rosuvastatin both on lipids profile and gene expression of peripheral leukocytes following therapy with a single dose of rosuvastatin.


METHODS
Thirty healthy Chinese male volunteers were enrolled. The serum lipids, high-sensitivity C-reactive protein, and plasma fibrinogen were determined before and 72 hours after administration of 20 mg of rosuvastatin. The differentially expressed genes of peripheral leukocytes after administration of rosuvastatin were screened using human oligonucleotide microarray gene expression chips. Then four of the differentially expressed genes including ATM, CASP8, IL8RB and S100B were verified by real-time polymerase chain reaction (PCR).


RESULTS
Rosuvastatin decreased both serum total cholesterol and low-density lipoprotein cholesterol significantly 72 hours after administration of a single dose of 20 mg rosuvastatin. However, no significant changes occurred in blood high-density lipoprotein cholesterol, triglycerides, C-reactive protein and fibrinogen after the treatment. A total of 24 genes were differentially expressed after the treatment. They were involved in important cell biological processes such as cytokine-cytokine receptor interaction, apoptosis signaling, etc.


CONCLUSIONS
Rosuvastatin rapidly modulates the serum lipids and affects the gene expression of peripheral leukocytes in healthy volunteers. This finding provides some new clues for further studies on its potential pleiotropic effects.
Hua
Cong-xiao
CX
Key Laboratory of Clinical Trial Research in Cardiovascular Drugs, Ministry of Health, Beijing Fuwai Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Li
Yi-shi
YS
Liu
Yu-qing
YQ
Liu
Hong
H
Li
Na
N
Wu
Ying
Y
Xu
Li
L
Huang
Yi-ling
YL
D000328:Adult; D053181:Caspase 8 / Q000235:genetics; D005464:Fluorobenzenes / Q000494:pharmacology*; D020869:Gene Expression Profiling; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D008055:Lipids / Q000097:blood*; D008297:Male; D016133:Polymerase Chain Reaction; D011743:Pyrimidines / Q000494:pharmacology*; D053700:Receptors, Interleukin-8 / Q000235:genetics; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology*
D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D011743:Pyrimidines; D053700:Receptors, Interleukin-8; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; D053181:Caspase 8