| Diabetes Mellitus (DM) is strongly correlated with ischemic stroke, and it has also been shown to be an important and independent risk factor for stroke. The mechanism of diabetic cerebral infarction is not definitively established. Furthermore, the diabetic cerebrovascular disease is associated not only with some abnormalities known to increase the risk for atherosclerosis, such as hyperglycemia, hypertension, dyslipidemia and smoking habits, but also with alterations in coagulability and fibrinolysis, ethnic factor, etc. Plasminogen activator inhibitor type-1 (PAI-1) plays a regulatory role in the plasminogen activator system (PAs), and is the primary physiologic inhibitor of plasminogen activation in blood. PAI-1 is a single-chain glycoprotein with a molecular weight of 52000 Da and consists of 379 amino acids. Endogenous t-PA is rapidly neutralized by PAI-1, which binds to t-PA and forms a stable 1:1 complex. In case of elevated PAI-1 level, the action of fibrinolysis is depressed, which results in thrombus formation and contributes to the development and the clinical course of thromboembolic diseases. Elevated PAI-1 level has been observed in patients with obesity and diabetes, suggesting PAI-1, as a risk factor for thrombus formation, is involved in atherothrombotic process. Impaired fibrinolysis may play a crucial role in atherogenesis, predisposing diabetic patients to micro and macrovascular complications. PAI-1, as a key inhibitor in fibrinolysis system, which plasma levels and activity depend on the one hand on gene regulation but are related on the other hand to metabolic determinants such as BMI, TG, FPI. Polymorphism in the PAI-1 gene promoter, a single guanosine insertion/deletion variation, has been shown to be related not only to elevated PAI-1 plasma levels but also to thromboembolic disorders. Study of relationship between PAI-1 gene polymorphisms and cerebral infarction in Chinese diabetic patients has not been reported up to now. The abnormal expression of PAI-1 in obesity might represent one of the mechanisms through which the risk for the development of cardio-cerebrovascular diseases is increased in obese individuals. The increase of body weight and body fat in obesity supports the presumption that adipose tissue is a potential source of plasma PAI-1, because the mass of fat is relevant to the number of adipocytes, and to the volume of the adipocyte as well. Therefore, the aim of the study was to investigate the correlation between genotype at a single nucleotide insertion/deletion (4G/5G) polymorphism in the promoter region of the PAI-1 gene and cerebral infarction (CI) in type 2 diabetes, or circulating PAI-1 levels in type 2 diabetes with and without cerebral CI; secondly, to study the relationship of PAI-1 antigen and some metabolic parameters such as BMI,TG,HbA1c,FPI. The purpose of our second part of work was to identify the locallization of PAI-1 synthesis in human adipose tissue sections by immunolocalization and in situ hybridization; to investigate the associations between changes in plasma PAI-1 and adipose tissue; to compare the levels of PAI-1 expression between omental and subcutaneous fat territories in obese or lean groups, and to explore the contribution of PAI-1 gene 4G/5G polymorphism to PAI-1 expression in human adipose tissue. Methods: 1. 280 subjects were divided into four groups according to the presence or absence of diabetes and CI, i.e. 92 healthy controls, 60 patients with CI, 88 patients with type 2 DM , 40 patients with type 2 DM and CI . Body height, weight, TG, TC, HbA1c and fasting plasma insulin levels were measured. PAI-1 antigen was measured with ELISA kit. The 4G/5G polymorphism in the PAI-1 gene promoter region were genotyped by allele specific PCR. The allele frequencies and genotypes in each group were scored and compared by Hardy-Weinberg equilibrium using a χ2 test. All analyses were performed according to the Excell 12000 statistical package. For all data, signifisance was established at P﹤0.05.
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