کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5944118 | 1172342 | 2015 | 13 صفحه PDF | دانلود رایگان |

- Lobeglitazone, a new PPARγ agonist, reduced neointimal formation significantly after balloon injury in rat carotid arteries.
- Lobeglitazone treatment reduced the atheromatous burden in the aorta of ApoEâ/â mice fed a high-fat and high-cholesterol diet.
- Lobeglitazone reduced adhesion of vascular cells, NF-κB p65 translocation, and improved atherosclerosis risk factors.
ObjectiveThe ligand-activated transcription factor peroxisome proliferator-activated receptor gamma (PPARγ) is a key factor in adipogenesis, insulin sensitivity, and cell cycle regulation. Activated PPARγ might also have anti-inflammatory and antiatherogenic properties. We tested whether lobeglitazone, a new PPARγ agonist, might protect against atherosclerosis.MethodsA rat model of balloon injury to the carotid artery, and high-fat, high-cholesterol diet-fed apolipoprotein E gene knockout (ApoEâ/â) mice were studied.ResultsAfter the balloon injury, lobeglitazone treatment (0.3 and 0.9 mg/kg) caused a significant decrease in the intima-media ratio compared with control rats (2.2 ± 0.9, 1.8 ± 0.8, vs. 3.3 ± 1.2, P < 0.01). Consistent with this, in ApoEâ/â mice fed a high-fat diet, lobeglitazone treatment (1, 3, and 10 mg/kg) for 8 weeks reduced atherosclerotic lesion sizes in the aorta compared with the control mice in a dose-dependent manner. Treatment of vascular smooth muscle cells with lobeglitazone inhibited proliferation and migration and blocked the cell cycle G0/G1 to S phase progression dose-dependently. In response to lobeglitazone, tumor necrosis factor alpha (TNFα)-induced monocyte-endothelial cell adhesion was decreased by downregulating the levels of adhesion molecules. TNFα-induced nuclear factor kappa-B (NF-κB) p65 translocation into the nucleus was also blocked in endothelial cells. Insulin resistance was decreased by lobeglitazone treatment. Circulating levels of high sensitivity C-reactive protein and monocyte chemoattractant protein-1 were decreased while adiponectin levels were increased by lobeglitazone in the high-fat diet-fed ApoEâ/â mice.ConclusionLobeglitazone has antiatherosclerotic properties and has potential for treating patients with diabetes and cardiovascular risk.
Journal: Atherosclerosis - Volume 243, Issue 1, November 2015, Pages 107-119