| The abrupt increased incidence of typeⅡdiabetes mellitusseriously threat human health, which is the third non-infectious diseasesstepping to the incidence of cardiovascular disease and tumor. The maincauses of the death and injury in diabetes mellitus(DM) have consideredas vascular diseases from now, most of which is atherosclerosis. AmericanHeart Association assorts DM into cardiac vascular diseases (CVD) in1999. According to American central for disease control (CDC), theincidence of DM in postmenopausal women is higher than premenopausalwomen. The lower estrogen can cause the dysfunction of endothelial cells.Some of the studies on hormone replacement therapy can put off and treatthe occurrence of cardiovascular diseases, which is on disputable.Nitric oxide is a vasorelaxation factor, which plays an important rolein normal relaxant and contracted function in endothelial cells. Moreover,it can inhibit the platelet aggregation and thrombosis, prevent the vascularsmooth muscle cell (VSMC) proliferation, and inhibit the vascularpermeability and the leucocytes adhesion, then to prevent theatherogenesis. NO is synthesised by the action of the enzyme nitric oxidesynthase (NOS), which oxidises the amino-acid L-arginine to generateL-citrulline and NO. NO synthase (NOS), which has three isoforms, neuronal NOS (nNOS/NOS-1), inducible NOS (iNOS/NOS-2) andendothelial NOS (eNOS/NOS-3). NOS-3 is expressed in platelets,endothelial cell, VSMC and renal tubular epithelial cell. It is modulated bydifferent factors in different cells, works through different pathway.Hypoinsulinism and insulin resistance induce the hyperglycemia indiabetes. The aldehyde and ketone group of glucose react with some freeend-amino acids of protein (Maillard reaction), to form the advancedglycation end-products (AGEs), which is the proinflammatory moleculesand accelerate the atherogenesis. Some of the studies indicated AGEscould influence endothelial functions by inhibiting NOS-3 expression, butwhether estrogen can reverse the inhibition should be further studied.Our purpose is to study if the lower concentration estrogen has therelationship to the diabetes and the change of NOS-3 in simulated diabetesin vitro and clinical female diabetes in vivo. In vitro experiments, wedetected the NOS-3 expression and activity after being treated the AGEs,17β-oestradiol, singly and the combination in human platelets.Intraplatelet cyclic GMP, an index of bioactive NO, was measured byradioimmunoassay. We found 17β-oestradiol is partially attenuates theinhibition of NOS-3 by AGEs in human platelets. The 17β-oestradiol isalso partially attenuates the increased platelet aggregation by AGEs. In theclinical research, we tested the change of lipid and glucose levels infemale and the change of NOS-3 level in platelet of the same subjects, we also found the NOS-3 phosphorylation expression and total NOS-3expression in human platelets in the postmenopausal women is lower thanpre-menopausal women. In this way, we infer the 17β-oestradiol ispartially attenuates the inhibition of NOS-3 by AGEs in human plateletsand the NOS-3 expression level in pre-menopausal women is higher thanpostmenopausal women.On our study indicated that the lower 17β-oestradiol level plays animportant role in diabetes in the postmenopausal women, NOS-3 may takepart in the mechanism.
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