PMID- 19641680
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20110714
LR  - 20211020
IS  - 1205-6626 (Print)
IS  - 1205-6626 (Linking)
VI  - 10
IP  - 3
DP  - 2005 Fall
TI  - Hyperhomocysteinemia exacerbates the development of intimal hyperplasia in 
      Sprague-Dawley rats: Alleviation by rosiglitazone.
PG  - 154-9
AB  - The amino acid intermediate homocysteine (Hcy) is formed during the metabolism of 
      methionine to cysteine. Hyperhomocysteinemia (HHcy) is recognized as an 
      independent risk factor for coronary atherosclerosis. The circulating levels of 
      total Hcy (tHcy) can increase due to intake of foods rich in methionine or 
      deficiencies of vitamins such as folate, pyridoxine and cyanocobalamin, which are 
      required for the metabolism of Hcy. In addition, mutations in the genes coding 
      for Hcy metabolizing enzymes can contribute to an increase in tHcy levels. 
      Clinical and epidemiological studies have shown that an elevated level of tHcy 
      measured in serum or plasma is a strong predictor of cardiovascular disease risk, 
      which appears to be greatest in patients who have HHcy following a methionine 
      load. Intimal hyperplasia (IH) (intima/media [I/M] ratio) is the universal 
      response of a vessel to injury and may result in vasoconstriction when left 
      unattended. The effect of dietary HHcy on balloon catheter-injured carotid artery 
      and its modulation (if any) by the peroxisome proliferator-activated receptor 
      agonist gamma rosiglitazone was evaluated in 12-week-old female Sprague-Dawley 
      rats fed either a control diet or a diet containing 1% L-methionine. Once the 
      rats were established on the diet, the group that was fed 1% L-methionine was 
      further subdivided and either given an aqueous preparation of 3 mg/kg/day 
      rosiglitazone or the vehicle via oral gavage for one week. This was followed by 
      surgically injuring the left carotid artery using a Maverick Over-The-Wire 
      catheter (2.0 mm x 20 mm, 3.2F; Boston Scientific, USA). The rats were continued 
      on their respective diets and drug regimen for 21 days postsurgery. On day 22 of 
      the procedure, the rats were sacrificed for collection of blood, the carotid 
      arteries and liver for biochemical and histological evaluation. Compared with 
      controls there was a significant increase in both tHcy levels and I/M ratio in 
      the rats fed 1% L-methionine (5.4+/-0.28 muM versus 32.8+/-3.01 muM, P<0.002; and 
      0.175+/-0.05 versus 1.05+/-0.23, P<0.005, respectively). The effect of 
      rosiglitazone in rats fed the control diet was not prominent. On the other hand, 
      administration of rosiglitazone to the rats on the 1% L-methionine diet 
      significantly reduced the levels of serum tHcy (16.6+/-2.1 muM versus 32.8+/-3.01 
      muM, P<0.001); however, the tHcy levels remained significantly elevated compared 
      with animals on the control diet (P<0.002). The group receiving the L-methionine 
      diet plus rosiglitazone had an inhibition in the development of IH compared with 
      those receiving the L-methionine diet alone (I/M of 0.278+/-0.041 versus 
      1.05+/-0.23, P<0.01). Moreover, the development of IH in the group receiving the 
      L-methionine diet plus rosiglitazone treatment was not significantly different 
      from that observed in the group on the control diet without rosiglitazone 
      (0.278+/-0.041 versus 0.175+/-0.05, respectively). These findings may have 
      important implications in deciphering the molecular mechanisms involved in the 
      augmentation of IH in HHcy and modulation of this process by rosiglitazone.
FAU - Murthy, Sn
AU  - Murthy S
AD  - Tulane University Health Sciences Center, New Orleans, Louisiana, USA.
FAU - Fonseca, Va
AU  - Fonseca V
FAU - McNamara, Db
AU  - McNamara D
LA  - eng
PT  - Journal Article
PL  - Canada
TA  - Exp Clin Cardiol
JT  - Experimental and clinical cardiology
JID - 9715903
PMC - PMC2716244
OTO - NOTNLM
OT  - Carotid
OT  - Hyperhomocysteinemia
OT  - Metabolism
OT  - Methionine
OT  - Vasoconstriction
EDAT- 2005/10/01 00:00
MHDA- 2005/10/01 00:01
PMCR- 2005/09/01
CRDT- 2009/07/31 09:00
PHST- 2009/07/31 09:00 [entrez]
PHST- 2005/10/01 00:00 [pubmed]
PHST- 2005/10/01 00:01 [medline]
PHST- 2005/09/01 00:00 [pmc-release]
AID - ecc10154 [pii]
PST - ppublish
SO  - Exp Clin Cardiol. 2005 Fall;10(3):154-9.