PMID- 15178560
OWN - NLM
STAT- MEDLINE
DCOM- 20050210
LR  - 20131121
IS  - 1524-4636 (Electronic)
IS  - 1079-5642 (Linking)
VI  - 24
IP  - 8
DP  - 2004 Aug
TI  - Cholesterol-lowering independent regression and stabilization of atherosclerotic 
      lesions by pravastatin and by antimonocyte chemoattractant protein-1 therapy in 
      nonhuman primates.
PG  - 1522-8
AB  - OBJECTIVE: Anti-atherosclerotic effects of statins might be mediated partly by 
      pleiotropic cholesterol-lowering independent mechanisms. We used nonhuman 
      primates and examined whether treatment with pravastatin or antimonocyte 
      chemoattractant protein-1 (MCP-1) therapy can induce regression and stabilization 
      of established atherosclerotic lesions through cholesterol-lowering independent 
      mechanisms. METHODS AND RESULTS: Advanced atherosclerosis was induced in the 
      abdominal aorta and the common iliac artery of cynomolgus monkeys by undergoing 
      balloon injury and giving atherogenic diet for 6 months. At 6 months, the diet 
      was changed to normal chow, and the animals were allocated to 4 treatment groups: 
      control vehicle group and other groups treated with pravastatin (1 or 10 mg/kg) 
      or with mutant MCP-1 gene transfection for additional 6 months. Each compound was 
      treated instead of the atherogenic diet, and cholesterol contents in 
      pravastatin-treated groups were adjusted to equalize plasma cholesterol level 
      among groups. Pravastatin reduced neointimal formation in the aorta, but not in 
      the common iliac artery. Pravastatin reduced intimal macrophage area and other 
      markers of plaque destabilization in the common iliac artery. Equivalent 
      inhibitory effects were observed in animals that received mutant MCP-1 gene 
      transfection. No serious side effects were noted by 2 therapeutic modalities. 
      CONCLUSIONS: This study demonstrated cholesterol-lowering independent regression 
      and stabilization of established atherosclerotic lesions by pravastatin and by 
      anti-MCP-1 therapy in nonhuman primates. An anti-inflammatory mechanism may be 
      involved in the beneficial effects of pravastatin.
FAU - Kitamoto, Shiro
AU  - Kitamoto S
AD  - Department of Cardiovascular Medicine, Graduate School of Medical Sciences, 
      Kyushu University, Fukuoka, Japan.
FAU - Nakano, Kaku
AU  - Nakano K
FAU - Hirouchi, Yasuhiko
AU  - Hirouchi Y
FAU - Kohjimoto, Yoshiro
AU  - Kohjimoto Y
FAU - Kitajima, Shunichi
AU  - Kitajima S
FAU - Usui, Makoto
AU  - Usui M
FAU - Inoue, Shujiro
AU  - Inoue S
FAU - Egashira, Kensuke
AU  - Egashira K
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20040603
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Anticholesteremic Agents)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 0 (DNA, Complementary)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Immunoglobulin M)
RN  - 11128-99-7 (Angiotensin II)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 3.4.15.1 (Peptidyl-Dipeptidase A)
RN  - EC 3.4.23.15 (Renin)
RN  - KXO2KT9N0G (Pravastatin)
SB  - IM
MH  - Angiotensin II/blood
MH  - Animals
MH  - Anti-Inflammatory Agents, Non-Steroidal/*pharmacology/therapeutic use
MH  - Anticholesteremic Agents/pharmacology/therapeutic use
MH  - Aorta, Abdominal/injuries/pathology
MH  - Aortic Diseases/blood/*drug therapy
MH  - Arteriosclerosis/blood/*drug therapy/etiology
MH  - Catheterization
MH  - Chemokine CCL2/antagonists & inhibitors/chemistry/*genetics/immunology
MH  - Chemotaxis
MH  - Cholesterol/blood
MH  - Cytokines/blood
MH  - DNA, Complementary/genetics
MH  - Diet, Atherogenic
MH  - Drug Evaluation, Preclinical
MH  - *Genetic Therapy
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacology/therapeutic use
MH  - Hypercholesterolemia/blood/complications/drug therapy
MH  - Iliac Artery/injuries/pathology
MH  - Immunoglobulin G/biosynthesis/immunology
MH  - Immunoglobulin M/biosynthesis/immunology
MH  - Inflammation
MH  - Macaca fascicularis
MH  - Male
MH  - Peptidyl-Dipeptidase A/blood
MH  - Phenotype
MH  - Pravastatin/*pharmacology/therapeutic use
MH  - Random Allocation
MH  - Renin/blood
MH  - Transfection
EDAT- 2004/06/05 05:00
MHDA- 2005/02/11 09:00
CRDT- 2004/06/05 05:00
PHST- 2004/06/05 05:00 [pubmed]
PHST- 2005/02/11 09:00 [medline]
PHST- 2004/06/05 05:00 [entrez]
AID - 01.ATV.0000134518.27241.da [pii]
AID - 10.1161/01.ATV.0000134518.27241.da [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 2004 Aug;24(8):1522-8. doi: 
      10.1161/01.ATV.0000134518.27241.da. Epub 2004 Jun 3.