| Endothelial dysfunction is a feature of pathologic physiology early atherosclerosis (AS) and is an important key factor in causing the occurring and progressing of AS and cardiovascular diseases. Overweight and obesity is an important risk factor to induce cardiovascular diseases, and frequently coexist with hypertension, hyperlipidemia, hyperglycemia and insulin resistance (IR) which was called as IR syndrome or metabolic syndrome (MS). In central obesity patients, the degree of abdominal obesity correlated significantly with the increasing and clustering cardiovascular risk factors. Endothelial dysfunction possible resulted from obesity is the key mechanism in causing the above abnormality. The endothelial dysfunction in subjects with overweight and obesity could induce or accelerate AS and promote the occurring and progressing of metabolic and cardiovascular diseases which correlated with obesity.Present studies revealed that the activating of endothelium cell was a primary cell mechanism. Endothelial dysfunction results from the interaction through a series of complex heredity, environment and other factors as cigarette products, free radicals, oxidized lipoproteins, hyperglycemia, hypertriglyceridemia and shear stress and the interaction if which may cause a series of dysfunctions including IR and the other manifestations of metabolic syndrome. Central obesity and IR are cardiovascular risk factors, and both are closely related. Among them, the endothelial dysfunction possible caused by obesity may be a key link in the forming of IR and the occurring and clustering of cardiovascular risk factors. Up to now, it is still short of the investigation data of large sample for the effects of overweight and obesity on endothelial function. Thepathogenesis of endothelial dysfunction, especially molecular pathogenesis in overweight and obesity subjects is still unknown in detail though have some study for it and the relation between it and IR. It is necessary to make further clarify the relations of endothelial dysfunction to IR and cardiovascular factors and the effects of its on clustering of obesity-related cardiovascular risk factors compared with IR which is more important.3 3-adrenergic receptor (3 3-AR) is third ?-adrenergic receptor being found of late years. P 3-AR located mainly in adipocytes, especially brown adipocytes and is implicated in the regulation of thermogenesis and lipolysis. For this reason, the change of function in 3 3-AR could has effects on body weight and lipometabolism. Recently, a missense mutation replacing with arginine at codon 64 of the |3 3-AR gene was showed to be associated with abdominal obesity and IR and suggested this locus as a strong candidate for increased obesity and metabolic complications of obesity. Both increased body fat are risk factors of cardiovascular diseases and closely associated with endothelial dysfunction, therefore it is hypothesized that Trp64Arg mutation in the ?3-AR gene associated with endothelial dysfunction in overweight and obesity subjects and may be used as a genetic maker for visceral fat obesity and the metabolic syndrome. Endothelial dysfunction may play an important role in the clustering of cardiovascular risk factors and the occurring of MS.The objective of this study is as follows: (1) Explore molecular pathogenesis of endothelial function in overweight and obesity and effects of Trp64Arg mutation in?3-AR gene on obesity and MS through study of the relation between 0 3-AR gene Trp64Arg mutation and endothelial dysfunction in middle-aged subjects with overweight and obesity. (2) Further clarify the relation between endothelial dysfunction and IR, and explore the pathogenesis of endothelial dysfunction through investigation of the impacts of endothelial dysfunction and other factors on IR and insulin secretion function in overweight and obesity subjects. (3) Make further clear the role of endothelial dysfunction in occurring and clusteringof cardiovascular risk factors and the relationship between them.All subjects aged 35...
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