PMID- 15312879
OWN - NLM
STAT- MEDLINE
DCOM- 20040910
LR  - 20220228
IS  - 0735-1097 (Print)
IS  - 0735-1097 (Linking)
VI  - 44
IP  - 4
DP  - 2004 Aug 18
TI  - Effects of pravastatin on progression of glucose intolerance and cardiovascular 
      remodeling in a type II diabetes model.
PG  - 904-13
AB  - OBJECTIVES: We examined the effects of early treatment with a 
      3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor pravastatin on the 
      progression of glucose intolerance and cardiovascular remodeling in a model of 
      spontaneously developing type II diabetes mellitus (DM), the Otsuka Long-Evans 
      Tokushima Fatty (OLETF) rats. BACKGROUND: Clinical trials showed that pravastatin 
      prevented new-onset DM in hypercholesterolemic patients, and that it was 
      effective in prevention of cardiovascular events in diabetics. METHODS: The OLETF 
      rats were treated with pravastatin (100 mg/kg/day) from 5 weeks of age and 
      compared with age-matched untreated OLETF rats and normal Long-Evans Tokushima 
      Otsuka (LETO) rats on serial oral glucose tolerance tests (OGTT) and Doppler 
      echocardiography and on histopathological/biochemical analyses of the heart at 30 
      weeks. RESULTS: The OGTT revealed that 40% and 89% of untreated OLETF rats were 
      diabetic at 20 and 30 weeks, respectively, but 0% and only 30%, respectively, 
      were diabetic in the treated OLETF. Left ventricular diastolic function was found 
      impaired from 20 weeks in untreated OLETF but remained normal in the 
      treated-OLETF. The wall-to-lumen ratio and perivascular fibrosis of coronary 
      arteries were increased in untreated-OLETF but were limited in the treated-OLETF 
      at 30 weeks. Moreover, cardiac expressions of a fibrogenic growth factor, 
      transforming growth factor-beta1 (TGF-beta1), and a proinflammatory chemokine, 
      monocyte chemoattractant protein-1 (MCP-1), were increased in untreated-OLETF. 
      However, in the treated-OLETF, overexpressions of TGF-beta1 and MCP-1 were 
      attenuated, which was associated with overexpression of endothelial nitric oxide 
      synthase (eNOS) (2.5-fold of control LETO). CONCLUSIONS: Early pravastatin 
      treatment prevented cardiovascular remodeling in the spontaneous DM model by 
      retarding the progression of glucose intolerance, overexpressing cardiac eNOS, 
      and inhibiting overexpressions of fibrogenic/proinflammatory cytokines.
FAU - Yu, Yang
AU  - Yu Y
AD  - Second Department of Internal Medicine, Kagawa University School of Medicine, 
      Kita-gun, Japan.
FAU - Ohmori, Koji
AU  - Ohmori K
FAU - Chen, Yan
AU  - Chen Y
FAU - Sato, Chubun
AU  - Sato C
FAU - Kiyomoto, Hideyasu
AU  - Kiyomoto H
FAU - Shinomiya, Kaori
AU  - Shinomiya K
FAU - Takeuchi, Hiroto
AU  - Takeuchi H
FAU - Mizushige, Katsufumi
AU  - Mizushige K
FAU - Kohno, Masakazu
AU  - Kohno M
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Am Coll Cardiol
JT  - Journal of the American College of Cardiology
JID - 8301365
RN  - 0 (Blood Glucose)
RN  - 0 (Chemokine CCL2)
RN  - 0 (DNA Primers)
RN  - 0 (Insulin)
RN  - 0 (Leptin)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tgfb1 protein, rat)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (Triglycerides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 1.1.1.- (Hydroxymethylglutaryl CoA Reductases)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 1.14.13.39 (Nos3 protein, rat)
RN  - KXO2KT9N0G (Pravastatin)
SB  - IM
MH  - Animals
MH  - Blood Glucose/drug effects
MH  - Chemokine CCL2/genetics/metabolism
MH  - Cholesterol/blood
MH  - DNA Primers
MH  - Diabetes Mellitus, Type 2/blood/*drug therapy
MH  - Disease Models, Animal
MH  - Glucose Tolerance Test
MH  - Hydroxymethylglutaryl CoA Reductases/administration & dosage/*therapeutic use
MH  - Immunohistochemistry
MH  - Insulin/blood
MH  - Leptin/blood
MH  - Nitric Oxide Synthase/genetics/metabolism
MH  - Nitric Oxide Synthase Type III
MH  - Pravastatin/administration & dosage/*therapeutic use
MH  - RNA, Messenger/analysis
MH  - Rats
MH  - Rats, Inbred OLETF
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transforming Growth Factor beta/genetics/metabolism
MH  - Transforming Growth Factor beta1
MH  - Triglycerides/blood
MH  - Tumor Necrosis Factor-alpha
MH  - Ventricular Remodeling/*drug effects
EDAT- 2004/08/18 05:00
MHDA- 2004/09/11 05:00
CRDT- 2004/08/18 05:00
PHST- 2003/12/26 00:00 [received]
PHST- 2004/03/11 00:00 [revised]
PHST- 2004/04/13 00:00 [accepted]
PHST- 2004/08/18 05:00 [pubmed]
PHST- 2004/09/11 05:00 [medline]
PHST- 2004/08/18 05:00 [entrez]
AID - S0735-1097(04)01091-5 [pii]
AID - 10.1016/j.jacc.2004.04.050 [doi]
PST - ppublish
SO  - J Am Coll Cardiol. 2004 Aug 18;44(4):904-13. doi: 10.1016/j.jacc.2004.04.050.