title: Statins reduce levels of metalloproteinases in patients with carotid occlusive disease.
abstract: OBJECTIVE
  Pharmaceutical stabilization of an unstable low-grade carotid artery stenosis delays surgery and improve outcome. Statins can be used to reduce intimal media thickness. Our aim was to determine the clinical and biological effects of rosuvastatin on plaque stabilization or regression.
  
  
  METHODS
  Forty-two consecutive male patients presenting with an asymptomatic internal carotid artery plaque uniformly anechogenic (group 1) 40-50% lumen diameter reduction formed the basis of the study. A group of 35 patients affected with a uniformly echogenic carotid artery stenosis (40-50%) served as control (group 2). Patients were followed-up every 8-month for 2 years with B-mode ultrasonography and color imaging. A computed tomography angiography (CTA) was performed before the initiation of the study period and at the end to confirm plaque characteristics and the degree of stenosis. Ticlopidine (250 mg/day) and rosuvastatin (10 mg/day) were administered. One blood sample was drawn at every control to assess the release of matrix metallopoteinases (MMPs)-1, -2, -3, -9, tissue inhibitors of metalloproteinases (TIMPs)-1 and -2.
  
  
  RESULTS
  After the administration of rosuvastatin plasma level of MMP-1, -2, -3 and -9 significantly decreased in both groups (P<0.001). Conversely, plasma level of TIMP-1 and -2 significantly increased in both groups (P<0.001). B-mode ultrasonography and color imaging and CTA failed to demonstrate a stabilization or regression of uniformly anehogenic carotid plaque during follow-up.
  
  
  CONCLUSIONS
  Rosuvastatin decreases the plasma level of MMPs and increases those of TIMPs. However, neither progression nor stabilization of low-grade unstable carotid plaques was seen.
authors.affiliation: Department of Surgery "Pietro Valdoni", "Sapienza" University of Rome, Rome, Italy - paolo.sapienza@uniroma1.it.
authors.forename: P
authors.initials: P
authors.lastname: Sapienza
authors.forename: V
authors.initials: V
authors.lastname: Borrelli
authors.forename: A V
authors.initials: AV
authors.lastname: Sterpetti
authors.forename: D
authors.initials: D
authors.lastname: Biacchi
authors.forename: L
authors.initials: L
authors.lastname: Venturini
authors.forename: E
authors.initials: E
authors.lastname: Tartaglia
authors.forename: M
authors.initials: M
authors.lastname: Bononi
authors.forename: L
authors.initials: L
authors.lastname: Di Marzo
mesh_terms: D000368:Aged; D000792:Angiography / Q000379:methods; D058070:Asymptomatic Diseases; D016893:Carotid Stenosis / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology; D018450:Disease Progression; D016903:Drug Monitoring; D005464:Fluorobenzenes / Q000494:pharmacology*; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D008297:Male; D045726:Metalloproteases / Q000378:metabolism*; D008875:Middle Aged; D058226:Plaque, Atherosclerotic / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology; D011743:Pyrimidines / Q000494:pharmacology*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology*; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D014057:Tomography, X-Ray Computed / Q000379:methods; D016896:Treatment Outcome; D018615:Ultrasonography, Doppler, Color / Q000379:methods
chemical_list: D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D019714:Tissue Inhibitor of Metalloproteinases; D000068718:Rosuvastatin Calcium; D045726:Metalloproteases