Protective Effects Of PPAR-Gamma Agonist On Apoe^-/- Mice Vascular Endothelial Cell Injury And Atherosclerosis

ObjectiveWe investigated the protective effects of PPAR-gamma agonist PIO on Apoe-/-mice endothelial cell injury and atherosclerosis and its possible mechanism.Methods1) First, we fed Apoe-/- mice to eat high sugar high-fat diet for 8 weeks. Then we injected the mice with STZ to increase the blood sugar. Finally, we treated the mice with pioglitazone for 8 weeks.2) We detected LDL-C, CHO, and HDL-C in serum by a chemical method and detected serum AGEs by ELLIS A method.3) We detected advanced glycation end products receptor (RAGE) and intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and endothelial nitric oxide synthase (eNOS), mitogen activated protein kinase (MAPK), nuclear factor kappa B, tumor necrosis factor A (TNF-α), matrix metalloproteinase MMP-9 and adenosine monophosphate protein kinase (AMPK) by Western blot.4) We made aortic HE staining and oil red O staining to observe the aortic atherosclerotic plaques.Results1) Compared with the control group, we found that PPAR gamma agonist can reduce the serum LDL-C and CHO and increased HDL-C;2) Compared with the control group, the AGEs and RAGE were significantly reduced in the PIO treatment group3) PPAR gamma agonists can protect endothelial cells from injury, such as reducing the expression of VCAM-1 and ICAM-1 and increasing the expression of eNOS in vascular endothelial cells;4) PPAR gamma agonist can inhibit the activation of NF kappa B and the expression of TNF-a;5) PPAR gamma agonist PIO not only reduced the area of atherosclerotic plaque in the group of diabetic Apoe-/- mice, but also reduced the area of atherosclerotic plaque in the Apoe-/- mice without diabetes. And PPAR gamma agonist PIO can reduce the degradation of extracellular matrix of the matrix metalloproteinases (MMP-9)..ConclusionPPAR gamma agonist PIO can reduce blood sugar, low density lipoprotein cholesterol, high density lipoprotein. It protects Apoe-/- mice vascular endothelial cell damage, such as the reduction of adhesion molecules ICAM-1 and VCAM-1 production and increase the expression of eNOS. It can inhibit vascular inflammation and atherosclerosis by reducing the expression of NF kappa B and TNF-a.