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- Title
PPARγ in endothelial cells influences high fat diet-induced hypertension
- Authors
Nicol, Christopher J.; Adachi, Masahiro; Akiyama, Taro E.; Gonzalez, Frank J.
- Abstract
Background: Peroxisome proliferator-activated receptor γ (PPARγ) ligands improve human hypertension. However, the mechanism and site of this effect remains unknown, confounded by PPARγ expression in many cell types, including endothelial cells (ECs). Methods: To evaluate the vascular role of PPARγ we used a conditional null mouse model. Specific disruption of PPARγ in ECs was created by crossing Tie2-Cre+ transgenic (T2T+) and PPARγ-floxed (fl/fl) mice to generate PPARγ (fl/fl)T2T+ (PPARγ E-null) mice. Conscious 8- to 12-week-old congenic PPARγ (fl/fl)Cre− (wild type) and PPARγ E-null mice were examined for changes in systolic blood pressure (BP) and heart rate (HR), untreated, after 2 months of salt-loading (drinking water), and after treatment for 3 months with high fat (HF) diet alone or supplemented during the last 2 weeks with rosiglitazone (3 mg/kg/d). Results: Untreated PPARγ E-nulls were phenotypically indistinguishable from wild-type littermates. However, compared to similarly treated wild types, HF-treated PPARγ Ẽ-nulls had significantly elevated systolic BP not seen after normal diet or salt-loading. Despite sex-dependent baseline differences, salt-loaded and HF-treated PPARγ Ẽ-nulls of either sex had significantly elevated HR versus wild types. Interestingly, rosiglitazone improved serum insulin levels, but not HF diet-induced hypertension, in PPARγ Ẽ-null mice. Conclusions: These results suggest that PPARγ in ECs not only is an important regulator of hypertension and HR under stressed conditions mimicking those arising in type 2 diabetics, but also mediates the antihypertensive effects of rosiglitazone. These data add evidence supporting a beneficial role for PPARγ-specific ligands in the treatment of hypertension, and suggest therapeutic strategies targeting ECs may prove useful.
- Subjects
PEROXISOMES; HYPERTENSION; THERAPEUTICS; HEART diseases; ENDOCRINE diseases
- Publication
American Journal of Hypertension, 2005, Vol 18, Issue 4, p549
- ISSN
0895-7061
- Publication type
Article
- DOI
10.1016/j.amjhyper.2004.10.032