The Effects Of Daintian/AIF-1on Atherosclerosis Risk Factors, Homocystein And Plasminogen Activator Inhibitor-1

Atherosclerosis (AS) is a disease of large and medium-sized muscular arteries and ischaracterized by endothelial dysfunction, vascular inflammation, and the buidup if lipids,cholesterol, calcium, and cellular debris within the intima of the vessel wall. Thepathogenesis of AS is a complex process, involving the interaction of multiple factor.Recently, in addition of traditional risk factors, effects of hyperhomocysteinemia and theimbalance of Coagulation and Fibrinolysis System on atherosclerosis cause more andmore attentions.Daintain was isolated and characterized from porcine intestines, which is highlyhomologous with Allograft Inflammatory Factor-1(AIF-1) cloned from activatedmacrophages of rat atherosclerotic allogenic heart grafts, therefore, we call itDaintain/AIF-1. Our and others’ studies have shown that, Daintain/AIP-1plays animportant role in the occurrence and development of atherosclerosis.We have previously observed that Daintain/AIF-1could bind to Cystathinoineβ-synthase (CBS) in vitro, which is essential for metabolism of homocysteine (Hcy),suggesting that Daintain/AIF-1may affect Hcy concentration in blood. In addition, bloodof mice injected with Daintain/AIF-1via the tail vein coagulates more quickly thancontrol, indicating that Daintain/AIF-1may play a role in the balance of Coagulation andFibrinolysis System. Plasminogen activator inhibitor-1(PAI-1), an important regulatoryelement in fibrinolysis, is classified as an acute phase reactant. A number of inflammatorycytokines have been found to up-regulate the PAI-1expression.Effects of Daintain/AIF-1on Hcy and PAI-1were investigated in this study, here arethe results:1） Injecting Daintain/AIF-1into female Kunming mice via the tail vein increasedthe concentration of Hcy in serum, however, the activity of CBS had no signficant changewhen stimulated with Daiintain/AIF-1in our study. 2） PAI-1in plasma was significantly elevated in mice administrated Daintain/AIF-1by tail intravenous injection.3） Daintain/AIF-1stimulated PAI-1mRNA expression in human umbilical veinendothelial cells (HUVECs) and HepG2cells.4） Stimulation with high concentration of Hcy caused a significant increase of PAI-1mRNA expression in HUVECs, however, compared with Daintain/AIF-1or Hcystimulated respectively, there was no obvious change in HUVECs co-incubated withDaintain/AIF-1and Hcy.5） The expression level of Daintain/AIF-1in HUVECs had no significant changewhen stimulated with Hcy.Our results suggested that Daintain/AIF-1may promote the occurrence anddevelopment of atherosclerosis through increasing serum Hcy concentration andup-regulating PAI-1expression.