Countervailing vascular effects of rosiglitazone in high cardiovascular risk mice: role of oxidative stress and PRMT-1
Open accessAbstract
In the present study, we tested the hypothesis that the PPARγ (peroxisome-proliferator-activated receptor γ) activator rosiglitazone improves vascular structure and function in aged hyperhomocysteinaemic MTHFR (methylene tetrahydrofolate reductase) gene heterozygous knockout (mthfr+/−) mice fed a HCD (high-cholesterol diet), a model of high cardiovascular risk. One-year-old mthfr+/− mice were fed or not HCD (6 mg·kg−1 of body weight·day−1) and treated or not with rosiglitazone (20 mg·kg−1 of body weight·day−1) for 90 days and compared with wild-type mice. Endothelium-dependent relaxation of carotid arteries was significantly impaired (−40%) only in rosiglitazone-treated HCD-fed mthfr+/− mice. Carotid M/L (media-to-lumen ratio) and CSA (cross-sectional area) were increased (2-fold) in mthfr+/− mice fed or not HCD compared with wild-type mice (P<0.05). Rosiglitazone reduced M/L and CSA only in mthfr+/− mice fed a normal diet. Superoxide production was increased in mthfr+/− mice fed HCD treated or not with rosiglitazone, whereas plasma nitrite was decreased by rosiglitazone in mice fed or not HCD. PRMT-1 (protein arginine methyltransferase-1), involved in synthesis of the NO (nitric oxide) synthase inhibitor ADMA (asymmetric ω-NG,NG-dimethylarginine), and ADMA were increased only in rosiglitazone-treated HCD-fed mthfr+/− mice. Rosiglitazone had both beneficial and deleterious vascular effects in this animal model of high cardiovascular risk: it prevented carotid remodelling, but impaired endothelial function in part through enhanced oxidative stress and increased ADMA production in mice at high cardiovascular risk.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 52 · Cited by 15
- Authors
- Savoia, C., Ebrahimian, T., Lemarié, C. A., Paradis, P., Iglarz, M., Amiri, F., Javeshgani, D., & Schiffrin, E. L.
- Affiliations
- Jewish General Hospital (CA)
- Corresponding author
- Savoia, Carmine
- Ebrahimian, Talin
- Paradis, Pierre
- Iglarz, Marc
- Amiri, Farhad
- Javeshgani, Danesh
- Venue
- Clinical Science
- Publisher
- Portland Press Ltd.
- Published
- 2010-02-09
- Volume
- 118
- Issue
- 9
- Pages
- 583-592
- ISSN
- 0143-5221 (ISSN-L)
- 1470-8736
- OpenAlex
- W2040392843
- Cited by
- 15
- References
- 52
- Citations by year
- 2024: 1 · 2020: 1 · 2019: 1 · 2017: 1 · 2015: 3 · 2014: 1 · 2013: 1 · 2012: 3
- FWCI
- 1.33
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- other-oa
- Locations
- Clinical Science (publishedVersion, other-oa)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
- Funders
- Heart and Stroke Foundation of Canada
- Government of Canada
- Canadian Institutes of Health Research (82790)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
- Keywords
- rosiglitazone, PPARγ, hyperhomocysteinemia, high-cholesterol diet, high cardiovascular risk, vascular function, endothelial dysfunction, oxidative stress, superoxide production, nitric oxide synthase, asymmetric dimethylarginine, nitrite
- MeSH terms
- Rosiglitazone, Animals, Carotid Artery, Internal, Cholesterol, Cholesterol, Dietary, Disease Models, Animal, Drug Evaluation, Preclinical, Endothelium, Vascular, Female, Nitrites, Protein-Arginine N-Methyltransferases, Superoxides, Mice, Knockout, Oxidative Stress, Hyperhomocysteinemia, Methylenetetrahydrofolate Reductase (NADPH2), Thiazolidinediones, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
