Experimental And Clinical Investigations On The Relationship Of Tissue Factor With Atherosclerosis And Diabetes

Plague disruption with superimposed thrombosis is the main cause of acute coronary syndromes including unstable angina myocardial infarction and sudden cardiac death. Plague contents determines its thrombogenicity , and tissue factor(TF)is thought to play a key role. Diabetes is one of important risk factor for coronary heart disease.Hyperglycemia can cause microvascular disease. Improved blood-glucose control decreases the progression of diabetic microvascular disease, but the effect on macrovascular complications is unknown. There is concern that if the wide used sulphonylureas may increase cardiovascular mortality in patients with diabetes. There is few report on the role of statin that if it can reduce TF expression in hyperglycemia patients. Xuezhikang is a lipid lowering drug made in China, and its effect on TF is unknown now.An atherosclerosis diabetes rat model was established using hypercholesterole diet and streptozocin (STZ) in this study to evaluate (1) the effect of hyperglycemia on the plague of macrovascular and the expression of TF. (2) the function and safety of sulphonylureas . (3)the influence if statin (Pravastatin and Xuezhikang) on the plague and the expression of TF. (4) the interaction of Xuezhikang and Gliclazide. (5)Serum tissue factor in acute coronary syndrome and its relation to clinical variables was investigated.The result shows: (1)An atherosclerosis diabetes rat model was successfully established. (2)Pravastatin and Xuezhikang are similar to reduce hypercholesteremia compared to the model group (12. 73 + 2. 87mmol/L, 16. 43 +7. 22mmol/L vs 31. 6+ 9. 81mmol/L,P<0. 01), hypertriglyceride (0. 42 + 0. 06mmol/U 0. 55+0. 2mmol/L vs 0. 92 +0. 37mmol/L, P<0. 01), the expression of TF(0. 74 + 0. 15, 0.67 + 0.15, 1.05 + 0.1, P<0. 05) and the area of plague(0. 27 + 0. IK 0.26 + 0.08, 0.43 + 0.1, P<0.05).(3) Gliclazide neither lower blood glucose ofSTZ rat (17. 71 +10. 91mmol/L vs model group 17. 82+9. 82mmol/L) nor it reduce the express of TF in the aorta(0. 92 + 0. 15 vs 1. 05 + 0.1, P>0. 05) and area of plague(0. 43 + 0. 13 vs 0. 43+0. 1, P>0. 05), but it can reduce hypercholesteremia and hypertriglyceride slightly. (4) No interaction between Gliclazide and Xuezhikang tolower blood-glucose, Clolesterol and triglyceride. Thefunction of Xuezhikang reducing the expression of TF was attenuated by Gliclazide. (5) Gliclazide increases the mortality of atherosclerotic diabetic rat. (6) STZ-induced diabetes does not alter the atherosclerotic plague. (7) The level of TF was elevated inacute coronary syndrome (70. 75 + 49. 63pg/ml; 85. 49 + 85. 89pg/ml; 31.88 + 31. 10 pg/ml; 22. 02+11. 83 pg/ml for acute myocardial infarction, unstable angina pectoris, stable angina pectoris and control group respectively ) and correlated with the sum of stenosed coronaryarteries, neutrophil and APOA-I.Conclusion: (l) Pravastatin and Xuezhikang are similar to reduce hypercholesteremia, the expression of TF and the area of plague. (2)Gliclazide neither lower blood glucose of STZ rat nor it reduce the express of TF in the aorta and area of plague. Gliclazide increases the mortality of atherosclerotic diabetic rat. (3)STZ-induced diabetes does not alter the atherosclerotic plague. (4)The level of TF was elevated in acute coronarysyndrome and correlated with the sum of stenosed coronaryarteries, neutrophil and APOA-I.