- 作者：Bosa Mirjanic-Azaric ; Manfredi Rizzo ; Ljubomir Sormaz ; Darja Stojanovic ; Snezana Uletilovic ; Snezna Sodin-Semrl ; Katja Lakota ; Andrej Artenjak ; Janja Marc ; Darko Cerne
- 关键词：ACE ; angiotensin-converting enzyme ; cDNA ; complementary deoxyribonucleic acid ; CCL2 ; gene encoding monocyte chemoattractant protein-1 ; Ch ; total cholesterol ; CRP ; C-reactive protein ; EDTA ; ethylenediaminetetraacetic acid ; EMP ; endothelial microparticles
- 刊名：Clinical Biochemistry
- 出版年：2013
- 出版时间：October, 2013
- 年：2013
- 卷：46
- 期：15
- 页码：1526-1531
- 全文大小：547 K
Objective
Statin pleiotropy is still an evolving concept, and the lack of clarity on this subject is due at least in part to the lack of a definitive biomarker for statin pleiotropy. Using plasma mRNA analysis as a novel research tool for the non-invasive in vivo assessment of gene expression in vascular beds, we hypothesised that atorvastatin lowers the plasma mRNA level from statin pleiotropy-target genes, and the reduction is independent of the reduction of low-density lipoprotein cholesterol (LDL-C).Design and methods
Forty-four patients with stable angina received atorvastatin therapy (20 mg/day, 10 weeks). Plasma chemokine (C-C motif) ligand 2 (CCL2) and intercellular adhesion molecule-1 (ICAM1) mRNA levels and their protein concentrations (MCP-1, sICAM-1) were analysed before and after the treatment. Plasma vascular adhesion molecule-1 (sVCAM-1) concentrations were also analysed.
Results
Atorvastatin lowered plasma mRNA levels (CCL2: ? 31.76 % , p = 0.037; ICAM1: ? 34.09 % , p < 0.001) and MCP-1 protein concentration (? 18.88 % , p = 0.008) but did not lower sICAM-1 and sVCAM-1 protein concentrations, and the decreases appeared to be independent from the lowering of LDL-C. The plasma mRNA levels correlated with their protein concentrations following statin treatment only.
Conclusion
Our results significantly strengthen the clinical evidence in support of statin pleiotropy. Furthermore, this unique simultaneous measurement of plasma mRNAs and their protein concentrations offers an advanced non-invasive in vivo assessment of the circulation pathology.