PMID- 9857893
OWN - NLM
STAT- MEDLINE
DCOM- 19990105
LR  - 20190708
IS  - 0735-1097 (Print)
IS  - 0735-1097 (Linking)
VI  - 32
IP  - 7
DP  - 1998 Dec
TI  - HMG-CoA reductase inhibition by atorvastatin reduces neointimal inflammation in a 
      rabbit model of atherosclerosis.
PG  - 2057-64
AB  - OBJECTIVES: To study the effect of the 3-hydroxy-3-methylglutaryl coenzyme A 
      (HMG-CoA)-reductase inhibitor atorvastatin on the potential mechanisms involved 
      in the recruitment of monocytic cells into the vessel wall. BACKGROUND: 
      Inhibitors of HMG-CoA-reductase reduce cardiovascular mortality though the 
      mechanisms yet elucidated. Most ischemic events are secondary to disruption of 
      atherosclerotic plaques highly infiltrated by macrophages. METHODS: 
      Atherosclerosis was induced in the femoral arteries of rabbits by endothelial 
      damage and atherogenic diet for 4 weeks. Then, animals were switched to standard 
      chow and randomized to receive either no treatment or atorvastatin (5 mg/kg/d) 
      and killed after 4 weeks. RESULTS: Atorvastatin induced a significant reduction 
      in serum lipids and in lesion size. Arterial macrophage infiltration was 
      abolished by the treatment, and monocyte chemoattractant protein-1 (MCP-1) was 
      significantly diminished in the neointima and in the media. Nuclear factor 
      kappa-B (NF-kappaB) was activated in the 60% of the lesions, both in macrophages 
      and vascular smooth muscle cells (VSMC), of the untreated group while only in 30% 
      of the atorvastatin group. NF-kappaB activity was also lower in the uninjured 
      aorta and liver of treated compared with untreated rabbits. In cultured VSMC, 
      MCP-1 expression and NF-kappaB activity induced by tumor necrosis factor alpha 
      were downregulated by atorvastatin. CONCLUSIONS: In a rabbit atherosclerosis 
      model, atorvastatin diminishes the neointimal inflammation, and this could 
      contribute to the stabilization of the atherosclerotic plaque. This may be an 
      additional explanation for the reduction of acute ischemic events in patients 
      treated with statins.
FAU - Bustos, C
AU  - Bustos C
AD  - Fundacion Jimenez Diaz, Universidad Autonoma, Madrid, Spain.
FAU - Hernandez-Presa, M A
AU  - Hernandez-Presa MA
FAU - Ortego, M
AU  - Ortego M
FAU - Tunon, J
AU  - Tunon J
FAU - Ortega, L
AU  - Ortega L
FAU - Perez, F
AU  - Perez F
FAU - Diaz, C
AU  - Diaz C
FAU - Hernandez, G
AU  - Hernandez G
FAU - Egido, J
AU  - Egido J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Am Coll Cardiol
JT  - Journal of the American College of Cardiology
JID - 8301365
RN  - 0 (Chemokine CCL2)
RN  - 0 (Heptanoic Acids)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (NF-kappa B)
RN  - 0 (Pyrroles)
RN  - A0JWA85V8F (Atorvastatin)
SB  - IM
MH  - Animals
MH  - Atorvastatin
MH  - Chemokine CCL2/analysis
MH  - Coronary Artery Disease/*drug therapy/pathology
MH  - Disease Models, Animal
MH  - Evaluation Studies as Topic
MH  - Heptanoic Acids/pharmacology/*therapeutic use
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology/*therapeutic use
MH  - Inflammation
MH  - Male
MH  - NF-kappa B/metabolism
MH  - Pyrroles/pharmacology/*therapeutic use
MH  - Rabbits
MH  - Random Allocation
MH  - Tunica Intima/chemistry/*pathology
EDAT- 1998/12/19 00:00
MHDA- 1998/12/19 00:01
CRDT- 1998/12/19 00:00
PHST- 1998/12/19 00:00 [pubmed]
PHST- 1998/12/19 00:01 [medline]
PHST- 1998/12/19 00:00 [entrez]
AID - S0735-1097(98)00487-2 [pii]
AID - 10.1016/s0735-1097(98)00487-2 [doi]
PST - ppublish
SO  - J Am Coll Cardiol. 1998 Dec;32(7):2057-64. doi: 10.1016/s0735-1097(98)00487-2.