Activation of peroxisome proliferator-activated receptor-β/-δ (PPARβ/δ) prevents endothelial dysfunction in type 1 diabetic rats

Inhibition of TLR4 attenuates vascular dysfunction and oxidative stress in diabetic rats

“…It has been suggested that activation of TLR4 induces ROS production [59][60][61]. We [62,63] and others [64,65] have shown that the increased levels of ROS were found in various arteries isolated from STZ-induced diabetic rats. In the present study, we identified TLR4 as a critical component in mediating HG-induced ROS production.…”

Chronic peroxisome proliferator-activated receptorβ/δ agonist GW0742 prevents hypertension, vascular inflammatory and oxidative status, and endothelial dysfunction in diet-induced obesity

“…Thus, chronic GW0742 treatment reduced blood pressure and improved endothelial function in aortas from spontaneously hypertensive rats [17] and deoxicorticosterone salt hypertensive rats [18], independently of the systemic metabolic state. This ligand also increased acetylcholineinduced relaxation in aorta and small mesenteric arteries from streptozotocin-induced diabetic rats [19] without altering blood glucose levels. Moreover, direct effects of these agonists on vascular cells in culture have also been described.…”

“…expected that the antiobesity effect induced by GW0742 is important for its protective cardiovascular effects. However, we have reported changes in vascular function in other models unrelated to changes in body fat or body weight [17][18][19] and even in in-vitro studies [21], suggesting that direct vascular effects may also play a significant role. The main factors that impair endothelial function in obesity, such as increased blood pressure, hyperglycemia, insulin resistance, hypertriglyceridemia, and systemic inflammation, were normalized by PPARb activation.…”

NADPH oxidase deficiency underlies dysfunction of aged CD8+ Tregs

“…Proinflammatory transcription factors, such as NF-κB, activator protein 1 (AP-1), and members of the STAT family, have been implicated in inducing NOX expression and thus oxidative stress (58)(59)(60)(61). In addition, NOX expression is subject to negative regulation involving members of the PPAR family (62).…”