Center for Hypertension and Metabolic Diseases, Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042, China.
PPAR Res. 2011;2011:291656. doi: 10.1155/2011/291656. Epub 2011 Nov 22.
Vascular endothelial dysfunction has been demonstrated in metabolic syndrome (MS). Chronic administration of rosiglitazone ameliorates endothelial dysfunction through PPARγ-mediated metabolic improvements. Recently, studies suggested that single dose of rosiglitazone also has direct vascular effects, but the mechanisms remain uncertain. Here we established a diet-induced rat model of MS. The impaired vasorelaxation in MS rats was improved by incubating arteries with rosiglitazone for one hour. Importantly, this effect was blocked by either inhibition of PPARγ or PPARδ. In cultured endothelial cells, acute treatment with rosiglitazone increased the phosphorylation of Akt and eNOS and the production of NO. These effects were also abolished by inhibition of PPARγ, PPARδ, or PI3K. In conclusion, rosiglitazone improved endothelial function through both PPARγ- and PPARδ-mediated phosphorylation of Akt and eNOS, which might help to reconsider the complex effects and clinical applications of rosiglitazone.
血管内皮功能障碍在代谢综合征（MS）中已经得到证实。罗格列酮的慢性给药通过 PPARγ 介导的代谢改善来改善内皮功能障碍。最近的研究表明，单次给予罗格列酮也具有直接的血管作用，但机制仍不清楚。在这里，我们建立了一种饮食诱导的 MS 大鼠模型。用罗格列酮孵育动脉一小时可改善 MS 大鼠的血管舒张功能障碍。重要的是，这种作用被 PPARγ 或 PPARδ 的抑制所阻断。在培养的内皮细胞中，罗格列酮的急性处理增加了 Akt 和 eNOS 的磷酸化和 NO 的产生。这些作用也被 PPARγ、PPARδ 或 PI3K 的抑制所消除。总之，罗格列酮通过 Akt 和 eNOS 的 PPARγ 和 PPARδ 介导的磷酸化改善了内皮功能，这可能有助于重新考虑罗格列酮的复杂作用和临床应用。
