Intensive treatment with atorvastatin reduces inflammation in mononuclear cells and human atherosclerotic lesions in one month

• Published in: Stroke (1970) 2005-08, Vol.36 (8), p.1796-1800
• Main Authors: MARTFN-VENTURA, Jose Luis, BLANCO-COLIO, Luis Miguel, GOMEZ-HERNANDEZ, Almudena, MUNOZ-GARCIA, Begona, VEGA, Melina, SERRANO, Javier, ORTEGA, Luis, HERNANDEZ, Gonzalo, TUNON, José, EGIDO, Jesus
• Format: Article
• Language: English
• Subjects: Aged; Anti-Inflammatory Agents - pharmacology; Atherosclerosis (general aspects, experimental research); Atherosclerosis - drug therapy; Atorvastatin Calcium; Biological and medical sciences; Blood and lymphatic vessels; Blotting, Southern; Blotting, Western; Cardiology. Vascular system; Cardiovascular system; Carotid Arteries - pathology; Chemokine CCL2 - metabolism; Cyclooxygenase 2 - metabolism; Dinoprostone - blood; Enzyme-Linked Immunosorbent Assay; Female; Heptanoic Acids - therapeutic use; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Image Processing, Computer-Assisted; Immunohistochemistry; Inflammation - drug therapy; Leukocytes, Mononuclear - cytology; Leukocytes, Mononuclear - metabolism; Lipids; Male; Medical sciences; Middle Aged; Neurology; NF-kappa B - metabolism; Pharmacology. Drug treatments; Pyrroles - therapeutic use; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Vascular diseases and vascular malformations of the nervous system; Vasodilator agents. Cerebral vasodilators
• ISSN: 0039-2499; 1524-4628
• DOI: 10.1161/01.STR.0000174289.34110.b0

To investigate the effect of short-term high-dose atorvastatin on blood and plaque inflammation in patients with carotid stenosis. 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). 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. 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.