Activated Sphingosine1-phosphate Receptor Induce Angiogenesis Of The Myocardial Infarction Rat And The Change Of Sphingosine1-phosphate In Intensive Statin Therapy To Unstable Angina

Objective Angiogenesis, including vasculogenesis, refers to theformation of new blood vessels in the budding way on the basis of theoriginal vessels. Many cytokines,such as vascular endothelial growthfactor (VEGF), basic fibroblast growth factor (bFGF), have beenconfirmed to play a role in promoting angiogenesis after myocardialinfarction. Sphingosine1-phosphate (S1P) can promote angiogenes, playendothelial protection, inhibit smooth muscle cell migration, and alleviatemyocardial ischemia/reperfusion injury. NO approach has been reported toalleviate the myocardial ischemia after myocardial infarction and improveheart function. In this study, the mechanisms of angiogenesis induced byFTY720(S1P analogue) were researched in myocardial ischemia.In recent years, studies have found that statins and angiogenesis areclosely related,and the effect of statins on therapeutic angiogenesis belongsto the category of the pleiotropic effects of statins. Angiogenesis is a complex dynamic process. This part is a clinical study,researching on theinflunce of intensive statin therapy on the serum S1P concentration ofpatients with unstable angina pectoris (UA)Methods12female Sprague-Dawley rats were randomly dividedinto four groups:①Sham-operated group(SHAM group).②AMIgroup(control group). The LADS were ligated and0.6ml0.9%salt waterwere given to the rats by Intraperitoneal injection.③FTY720group(intervention group) LADS were ligated and1mg/（kg.d）FTY720were given to the rats by Intraperitoneal injection.④F+L group（combinedintervention group）.1mg/（kg.d） FTY720and15mg/（kg.d）L-NAMEwere given to the rats after LADs ligated. Each group was divided into twosubgroups,namely1week group and4week group, each group of16SDrats. Cardiac function was measured by carotid artery intubation, and serumS1P were measured at the same time,using ELISA Kit. Mycocardialcapillary density were observed by CD34immunochemical stain and NO incardiac tissue were measured by nitric oxide assay kit. Expression ofVEGF and bFGF in cardiac tissue were measured by immunochemicalstain and RT-PCR.80UA patients were divided into two groups,normal rosuvastatin dosegroup and rosuvastatin loading dose group. The normal dose groupreceived rosuvastatin10mg/d and loading dose group reeived rosuvastatin 20mg/d. Serum S1P was measured before medication,and on the24hoursand7th day after medicationResults VEGF and b-FGF mRNA and protein expression levels inFTY720groups were significantly higher than the other groups at1weekand4weeks post-AMI. And VEGF and b-FGF mRNA and proteinexpression levels in groups of1week post-AMI were much higher than thesame groups of4week post-AMI.2.The capillary density in ischemicmyocardium in FTY720groups were significantly higher than AMI groupsand F+L groups in two time points. And the capillary density at4weekspost-AMI were much higher than that at1weeks post-AMI.3.The NOlevel in ischemica myocardium of FTY720group was significantlyhigher than AMI group,but was much lower than F+L groups in both1week and4weeks post-AMI. The concentration of serum S1P in UApatients was increased with time after rosuvastatin intervention, especiallyintensive statin group.Conclusion FTY720could enhance angiogenesis by increasingtransplantation and expression of VEGF and b-FGF,improving theproduction of NO inischemic myocardium,and improve the cardiacfunction of AMI rats. Intensive statin therapy can improve the expressionof S1P in short term.