Countervailing vascular effects of rosiglitazone in high cardiovascular risk mice: Role of oxidative stress and PRMT-1

We tested the hypothesis that the PPAR-γ activator rosiglitazone improves vascular structure and function in aged hyperhomocysteinemic methylene tetrahydrofolate reductase gene (MTHFR) heterozygous knockout mice (mthfr^+/-) fed a high cholesterol diet (HCD), a model of high cardiovascular risk. One year-old mthfr^+/- were fed or not HCD (6 mg/Kg/day) and treated or not with rosiglitazone (20 mg/Kg/day) for 90 days, and compared to wild-type mice. Endothelium dependent relaxation of carotid arteries was significantly impaired (-40%) only in rosiglitazone treated HCD-fed mthfr^+/-. Carotid media-to-lumen ratio (M/L) and cross-sectional area (CSA) were increased (2-fold) in mthfr^+/- fed or not HCD compared to wild-type mice (P<0.05). Rosiglitazone reduced M/L and CSA only in mthfr^+/- fed a normal diet. Superoxide production was increased in mthfr^+/- fed HCD treated or not with rosiglitazone, whereas plasma nitrite was reduced by rosiglitazone in mice fed or not HCD. Protein arginine methyltransferase-1 (PRMT-1), involved in synthesis of the NO synthase inhibitor asymmetric dimethylarginine (ADMA), and ADMA were increased only in rosiglitazone-treated HCD-fed mthfr^+/-. Rosiglitazone had both beneficial and deleterious vascular effects in this animal model of high cardiovascular risk: it prevented carotid remodeling, but impaired endothelial function in part through enhanced oxidative stress and increased ADMA production in mice at high cardiovascular risk.

View original post here:
Countervailing vascular effects of rosiglitazone in high cardiovascular risk mice: Role of oxidative stress and PRMT-1

Tags: hcd, hypothesis, treated-or-not, were-increased

Related posts:

1. Obesity is the major contributor to vascular dysfunction and inflammation in high fat diet hypertensive rats
2. Relation of circulating progenitor cells to vascular function and oxidative stress with long term training and short term detraining in older men
3. High fat diet increases inflammation in the mouse colon
4. Effects of GIK (glucose-insulin-potassium) on stress-induced myocardial ischemia
5. Clopidogrel, independent of vascular P2Y12 receptor, improves the arterial function in small mesenteric arteries from Ang II-hypertensive rats

Related posts brought to you by Yet Another Related Posts Plugin.

• Previous Entry: Sentinelle Medical Inc. and Ultrasonix Medical Corporation Announce Distribution Partnership.
• Next Entry: Eradicating Ignorance