Atorvastatin in stable angina patients lowers CCL2 and ICAM1 expression: Pleiotropic evidence from plasma mRNA analyses

作者：Mirjanic Azaric Bosa; Rizzo Manfredi; Sormaz Ljubomir; Stojanovic Darja; Uletilovic Snezana; Sodin Semrl Snezna; Lakota Katja; Artenjak Andrej; Marc Janja; Cerne Darko^*

来源：Clinical Biochemistry, 2013, 46(15): 1526-1531.

DOI：10.1016/j.clinbiochem.2013.06.006

• Atorvastatin
• CCL2
• ICAM1
• Interventional trial
• mRNA in plasma
• Pleiotropic effects

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). %26lt;br%26gt;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. %26lt;br%26gt;Results: Atorvastatin lowered plasma mRNA levels (CCL2: -31.76%, p = 0.037; ICAM1: -34.09%, p %26lt; 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. %26lt;br%26gt;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.

• 出版日期2013-10