PMID- 15877295
OWN - NLM
STAT- MEDLINE
DCOM- 20050630
LR  - 20181201
IS  - 0026-0495 (Print)
IS  - 0026-0495 (Linking)
VI  - 54
IP  - 5
DP  - 2005 May
TI  - Rosiglitazone reduces serum homocysteine levels, smooth muscle proliferation, and 
      intimal hyperplasia in Sprague-Dawley rats fed a high methionine diet.
PG  - 645-52
AB  - Homocysteine (Hcy) is a metabolite of the essential amino acid methionine. 
      Hyperhomocysteinemia is associated with vascular disease, particularly carotid 
      stenosis. Rosiglitazone, a ligand of the peroxisome proliferator-activated 
      receptor gamma , attenuates balloon catheter-induced carotid intimal hyperplasia 
      in type 2 diabetic rats. We studied 4 groups (n = 7 per group) of adult female 
      Sprague-Dawley rats fed (a) powdered laboratory chow (control), (b) control diet 
      with rosiglitazone (3.0 mg/kg/d), (c) diet containing 1.0% l -methionine, and (d) 
      diet containing methionine and rosiglitazone. After 1 week on high methionine 
      diet, the rats were administered an aqueous preparation of rosiglitazone by oral 
      gavage. One week after initiation of rosiglitazone, balloon catheter injury of 
      the carotid artery was carried out using established methods, and the animals 
      continued on their respective dietary and drug regimens for another 21 days. At 
      the end of the experimental period, blood samples were collected, and carotid 
      arteries and liver were harvested. Serum Hcy increased significantly on 
      methionine diet compared with controls (28.9 +/- 3.2 vs 6.3 +/- 0.04 micromol/L). 
      Development of intimal hyperplasia was 4-fold higher in methionine-fed rats; this 
      augmentation was significantly reduced ( P < .018) in rosiglitazone-treated 
      animals. Rosiglitazone treatment significantly ( P < .001) suppressed Hcy levels 
      and increased the activity of the Hcy metabolizing enzyme, 
      cystathionine-beta-synthase in the liver samples. Hcy (100 micromol/L) produced a 
      3-fold increase in proliferation of rat aortic vascular smooth muscle cells; this 
      augmentation was inhibited by incorporating rosiglitazone (10 micromol/L). After 
      balloon catheter injury to the carotid artery of animals on a high methionine 
      diet, there was an increase in the rate of development of intimal hyperplasia 
      consistent with the known effects of Hcy. It is demonstrated for the first time 
      that the peroxisome proliferator-activated receptor gamma agonist rosiglitazone 
      can attenuate the Hcy-stimulated increase in the rate of development of intimal 
      hyperplasia indirectly by increasing the rate of catabolism of Hcy by 
      cystathionine-beta-synthase and directly by inhibiting vascular smooth muscle 
      cell proliferation. These findings may have important implications for the 
      prevention of cardiovascular disease and events in patients with 
      hyperhomocysteinemia (HHcy).
FAU - Murthy, Subramanyam N
AU  - Murthy SN
AD  - Section of Endocrinology, Department of Medicine, Tulane University Health 
      Sciences Center, New Orleans, LA 70112, USA.
FAU - Obregon, Demian F
AU  - Obregon DF
FAU - Chattergoon, Natasha N
AU  - Chattergoon NN
FAU - Fonseca, Neil A
AU  - Fonseca NA
FAU - Mondal, Debasis
AU  - Mondal D
FAU - Dunne, Jeffrey B
AU  - Dunne JB
FAU - Diez, Jose G
AU  - Diez JG
FAU - Jeter, James R Jr
AU  - Jeter JR Jr
FAU - Kadowitz, Philip J
AU  - Kadowitz PJ
FAU - Agrawal, Krishna C
AU  - Agrawal KC
FAU - McNamara, Dennis B
AU  - McNamara DB
FAU - Fonseca, Vivian A
AU  - Fonseca VA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Metabolism
JT  - Metabolism: clinical and experimental
JID - 0375267
RN  - 0 (Ligands)
RN  - 0 (PPAR gamma)
RN  - 0 (Thiazolidinediones)
RN  - 05V02F2KDG (Rosiglitazone)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 9007-49-2 (DNA)
RN  - AE28F7PNPL (Methionine)
RN  - EC 4.2.1.22 (Cystathionine beta-Synthase)
SB  - IM
MH  - Animals
MH  - Carotid Arteries
MH  - Catheterization/*adverse effects
MH  - Cell Division/drug effects
MH  - Cystathionine beta-Synthase/metabolism
MH  - DNA/biosynthesis
MH  - Diet
MH  - Female
MH  - Homocysteine/antagonists & inhibitors/*blood
MH  - Hyperplasia
MH  - Ligands
MH  - Liver/enzymology
MH  - Methionine/*administration & dosage/pharmacology
MH  - Muscle, Smooth, Vascular/metabolism/*pathology
MH  - Myocytes, Smooth Muscle/metabolism/pathology
MH  - PPAR gamma/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Rosiglitazone
MH  - Thiazolidinediones/administration & dosage/metabolism/*pharmacology
MH  - Tunica Intima/drug effects/*pathology
EDAT- 2005/05/07 09:00
MHDA- 2005/07/01 09:00
CRDT- 2005/05/07 09:00
PHST- 2005/05/07 09:00 [pubmed]
PHST- 2005/07/01 09:00 [medline]
PHST- 2005/05/07 09:00 [entrez]
AID - S0026049505000089 [pii]
AID - 10.1016/j.metabol.2004.12.008 [doi]
PST - ppublish
SO  - Metabolism. 2005 May;54(5):645-52. doi: 10.1016/j.metabol.2004.12.008.