《脂代谢紊乱与动脉粥样硬化》ppt课件.ppt

Figure 95?Activated PPARa blocks the AP-1 signalling pathway by inhibiting the activation of AP-1, thus reducing endothelin-1 (ET-1) gene expression. KW: PPAR alpha, endothelin-1, ET-1, AP-1 * Figure 96 Fenofibric acid reduces ET-1 expression in a dose-dependent manner. KW: PPAR alpha, endothelin-1, ET-1, fibrate * Figure 97?Activated PPARa also reduces TF production by inhibition of NFkB and AP-1 activation. Decreased TF production reduces the state of hypercoagulability in the vicinity of the AS plaque. KW: PPAR alpha, tissue factor, NF-kB, AP-1 * Figure 98?Activated macrophages secrete cytokines (IL-6), which stimulate fibrinogen production. PPARa agonists block the IL-6 responsive element and reduce cytokine synthesis with a corresponding decrease in plasma fibrinogen concentrations. This effect of PPARa agonists is dose dependent. KW: PPAR alpha, fibrate, fibrinogen * Figure 99?Statins inhibit HMG-CoA reductase and block the cholesterol synthesis pathway. Decreased cellular cholesterol production induces activation of sterol regulatory element binding protein (SREBP), a transcription factor, particularly in hepatocytes. SREBP activation induces increased LDL receptor production and thus increased clearance of LDL from the blood. KW: statin, HMG-CoA reductase inhibitor, SREBP, LDL receptor, LDL * Figure 100?Sterol regulatory element binding protein is usually located on the endoplasmic reticulum (ER). Low levels of intracellular cholesterol induce cleavage of SREBP at two points on the molecule. This gives rise to the active form of SREBP, which detaches from the ER and migrates to the nucleus, where it activates LDL receptor gene expression. KW: statin, HMG-CoA reductase inhibitor, SREBP, LDL receptor, LDL * Figure 101?Statins also have similar effects to fibrates in relation to endothelial dysfunction, thrombogenicity and vascular inflammation. KW: statin, HMG-CoA reductase inhibitor, PPAR alpha, fibrate * Figure 102?It has been demonstrat