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

描述 首席研究人员建议检验雌激素是否 通过生产作为血管内皮损伤的保护剂 生长因子，肝素结合EGF(HB-EGF)，它反过来刺激 内皮依赖性松弛因子NO的产生。她会的 首先确定NO合成酶III的消息水平是否增加 人脐静脉内皮细胞(HUVEC)经维甲酸处理后 外源性HB-EGF。将建立一个时间进程，以刺激 NOS III mRNA和NOS III蛋白的表达。接下来，她将研究雌激素是否 细胞处理刺激HB-EGF和NOS III的产生 MRNAs。如果发现了效果，那么雌激素拮抗剂的效果将 被研究以确定雌激素是否通过其受体起作用。vbl.使用 申请者将研究Lyso PC作为“氧化脂质”的模型 慢性雌激素治疗是否会减弱HB-EGF的刺激作用 氧化脂质所致的NOS III。 该项目的目标是确定HB-EGF是否可以作为一种诊断 内皮功能障碍的生物标志物，以及它是否在 通过调节一氧化氮合酶III的表达实现内皮依赖性一氧化氮的产生。

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.