title: Atorvastatin in stable angina patients lowers CCL2 and ICAM1 expression: pleiotropic evidence from plasma mRNA analyses.
abstract: 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).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Clinical Centre Banja Luka, Department of laboratory diagnostics Banja Luka, Republic of Srpska, Bosnia and Herzegovina.
authors.forename: Bosa
authors.initials: B
authors.lastname: Mirjanic-Azaric
authors.forename: Manfredi
authors.initials: M
authors.lastname: Rizzo
authors.forename: Ljubomir
authors.initials: L
authors.lastname: Sormaz
authors.forename: Darja
authors.initials: D
authors.lastname: Stojanovic
authors.forename: Snezana
authors.initials: S
authors.lastname: Uletilovic
authors.forename: Snezna
authors.initials: S
authors.lastname: Sodin-Semrl
authors.forename: Katja
authors.initials: K
authors.lastname: Lakota
authors.forename: Andrej
authors.initials: A
authors.lastname: Artenjak
authors.forename: Janja
authors.initials: J
authors.lastname: Marc
authors.forename: Darko
authors.initials: D
authors.lastname: Cerne
mesh_terms: D000368:Aged; D060050:Angina, Stable / Q000097:blood / Q000188:drug therapy*; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000069059:Atorvastatin; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000097:blood / Q000235:genetics*; D008078:Cholesterol, LDL / Q000037:antagonists & inhibitors / Q000097:blood; D004334:Drug Administration Schedule; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors* / Q000097:blood / Q000235:genetics
chemical_list: D000924:Anticholesteremic Agents; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; C573420:ICAM1 protein, human; D011758:Pyrroles; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D000069059:Atorvastatin
keywords: 3-hydroxy-3-methylglutaryl coenzyme A; ACE; Atorvastatin; C-reactive protein; CCL2; CRP; Ch; EDTA; EMP; GAPDH; HDL-C; HMG-CoA; ICAM1; IMT; Interventional trial; LDL-C; MCP-1; Pleiotropic effects; SA; SAA; TG; angiotensin-converting enzyme; cDNA; carotid intima-media thickness; complementary deoxyribonucleic acid; endothelial microparticles; ethylenediaminetetraacetic acid; gene encoding glyceraldehyde-3-phosphate dehydrogenase; gene encoding intercellular adhesion molecule-1; gene encoding monocyte chemoattractant protein-1; high density lipoprotein cholesterol; low-density lipoprotein cholesterol; mRNA; mRNA in plasma; messenger ribonucleic acid; monocyte chemoattractant protein-1; sICAM-1; sVCAM-1; serum amyloid A; soluble intercellular adhesion molecule-1; soluble vascular cell adhesion molecule-1; stable angina; total cholesterol; triglycerides