Intensive treatment with atorvastatin reduces inflammation in mononuclear cells and human atherosclerotic lesions in one month.
OBJECTIVE
To investigate the effect of short-term high-dose atorvastatin on blood and plaque inflammation in patients with carotid stenosis.


METHODS
Twenty patients undergoing carotid endarterectomy without previous statin treatment were randomized to receive either atorvastatin 80 mg/d (n=11) or no statins (n=9) for 1 month. We studied inflammatory mediators in plasma (enzyme-linked immunosorbent assay), peripheral blood mononuclear cells (PBMCs; quantitative RT-PCR and EMSA) and plaques (immunohistochemistry and Southwestern histochemistry).


RESULTS
Atorvastatin significantly decreased total and low-density lipoprotein cholesterol and prostaglandin E2 plasma levels. PBMCs from treated patients showed impaired NF-kappaB activation and MCP-1 and COX-2 mRNA expression. Carotid atherosclerotic plaques demonstrated a significant reduction in macrophage infiltration, activated NF-kappaB, and COX-2 and MCP-1 expression.


CONCLUSIONS
Intensive treatment with atorvastatin decreases inflammatory activity of PBMCs and carotid atherosclerotic plaques in 1 month. These data strongly suggest that the antiinflammatory effect of high doses of statins in humans can be seen very early.
Martín-Ventura
Jose Luis
JL
Vascular Research Laboratory, Fundación Jiménez Díaz, Autónoma University, Madrid, Spain.
Blanco-Colio
Luis Miguel
LM
Gómez-Hernández
Almudena
A
Muñoz-García
Begoña
B
Vega
Melina
M
Serrano
Javier
J
Ortega
Luis
L
Hernández
Gonzalo
G
Tuñón
José
J
Egido
Jesús
J
D000368:Aged; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D050197:Atherosclerosis / Q000188:drug therapy*; D000069059:Atorvastatin; D015139:Blotting, Southern; D015153:Blotting, Western; D002339:Carotid Arteries / Q000473:pathology; D018932:Chemokine CCL2 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007249:Inflammation / Q000188:drug therapy*; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000378:metabolism; D008055:Lipids; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D011758:Pyrroles / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000893:Anti-Inflammatory Agents; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D016328:NF-kappa B; D011758:Pyrroles; D012333:RNA, Messenger; D000069059:Atorvastatin; D051546:Cyclooxygenase 2; D015232:Dinoprostone