HB EGF AS A BIOMARKER OF THE ENDOTHELIUM-DEPENDENT NO PA

描述 首席研究员提出要检验雌激素 作为保护剂，通过产生 肝素结合EGF（HB-EGF），这反过来又刺激 内皮依赖性舒张因子NO的产生。 她将 首先确定NO合酶III的信息水平是否增加 在人脐静脉内皮细胞（HUVEC）用 外源性HB-EGF 将建立一个时间进程，以刺激 NOS Ⅲ mRNA和NOS Ⅲ蛋白。 下一步她将研究雌激素 细胞的处理刺激HB-EGF和NOS III的产生 mRNA。 如果发现有作用，那么雌激素拮抗剂的作用将 研究雌激素是否通过其受体起作用。 使用 申请人将研究溶血PC作为“氧化脂质”模型 慢性雌激素治疗是否会减弱HB-EGF的刺激 和NOS III的氧化脂质。 该项目的目标是确定HB-EGF是否作为诊断 内皮功能障碍的生物标志物，如果它在 通过调节NOS III的表达来调节内皮依赖性NO的产生。

DESCRIPTION The principal investigator proposes to test the hypothesis that estrogens act as protective agents against endothelial damage through the production of the growth factor, heparin-binding EGF (HB-EGF), which in turn stimulates the production of NO, the endothelium dependent relaxation factor. She will first determine whether the message levels for NO synthase III are increased after the treatment of human umbilical vein endothelial cells (HUVEC) with exogenous HB-EGF. A time course will be established for the stimulation of NOS III mRNA and NOS III protein. Next she will study whether estrogen treatment of the cells stimulates the production of both HB-EGF and NOS III mRNAs. If effects are found, then the effect of an estrogen antagonist will be studied to determine if estrogen is acting through its receptor. Using lyso PC as a model for 'oxidized lipid' the applicant will investigate whether chronic estrogen treatment will attenuate the stimulation of HB-EGF and NOS III by the oxidized lipids. The goal of the project is to determine if HB-EGF serves as as a diagnostic biomarker for dysfunctional endothelium, and if it plays a role in endothelium-dependent NO production by regulating expression of NOS III.