血管活性肽在血管平滑肌细胞中的表达与调控机制

发布时间：2018-04-09 14:36

本文选题：血管平滑肌细胞　切入点：血管活性肽　出处：《河北医科大学》2005年博士论文

【摘要】：血管活性肽是一类调节血管平滑肌细胞(vascular smooth muscle cell,VSMC)舒缩功能、维持血管张力的小分子肽类物质,多数以自分泌、旁分泌方式发挥作用,按其血管效应的不同分为缩血管肽和舒血管肽。前者包括血管紧张素I(Iangiotensin II,Ang II)和内皮素-1(endothelin-1,ET-1)等,后者包括肾上腺髓质素(adrenomedullin,ADM)和心钠素(atrial natriuretic factor,ANF)等。生理条件下,血管舒-缩活性肽的分泌和生物活性处于动态平衡,以保证血管张力的稳态。不同种类的活性肽之间存在着复杂的正反馈或负反馈调节,由此构成一个精细、严密的血管张力调控网络。由于大多数缩血管活性肽具有强烈的促进VSMC 肥大、增殖、迁移的活性,其功能的亢进常常是多种血管重塑性疾病的主要诱因。而舒血管活性肽则具有相反的作用。因此,研究血管活性肽之间形成的复杂网络,阐明该网络对血管功能的调节机制,将有利于深层次了解血管活性肽系统的生理功能和在心血管疾病发生发展中的病理生理学意义。本研究课题以Ang II 为诱发因素,观察其对VSMC 释放ET-1、Ang II、ANF 和ADM 的影响及相互关系,研究了转录激活蛋白-1(activator protein-1,AP-1)和Janus 蛋白酪氨酸激酶-信号转导及转录激活因子途径( janus protein tyrosine kinase-signal transducers and activators of transcription pathway,JAK-STAT pathway)对血管活性肽基因转录激活的作用以及AP-1 和信号转导及转录激活因子5(signal transducers and activators of transcription 5,STAT5)在调节基因转录过程中的相互关系,以期揭示Ang II 对4 种血管活性肽相对水平调节的分子机制。 1 血管舒-缩肽在血管平滑肌细胞中的表达与调控研究基因序列分析证实,在Ang II、ET-1、ANF 和ADM 基因的启动子区中均含有AP-1的结合位点,而且,这4种血管活性肽的表达也有赖于AP-1的活化。本部分实验探讨了AP-1 的DNA 结合活性与4 种血管活性肽表达及其动态平衡之间的关系以及VSMC 在该网络平衡中的地位,并揭示Ang II 对4 种血管活性肽相对水平调节的分子机制。实验结果如下:
[Abstract]:Vasoactive peptides are small molecular peptides that regulate the vasomotor function of vascular smooth muscle cells (VSMC) and maintain vascular tension. Most of them act as autocrine and paracrine.The vasoconstrictor peptide and vasodilator peptide were divided into two groups according to their vascular effects.The former included angiotensin I(Iangiotensin IIG and endothelin-1 endothelin-1 et al. The latter included adrenomedullin adrenomedullin (ADM) and atrial natriuretic factor factor (ANFA).Under physiological conditions, the secretion and bioactivity of vasomotor active peptide were in a dynamic balance to ensure the steady state of vascular tension.There are complex positive or negative feedback regulation between different kinds of active peptides, which constitute a fine, tight vascular tension regulation network.Because most vasoconstrictive peptides have the activity of promoting hypertrophy, proliferation and migration of VSMC, the hyperactivity of vasoconstrictive peptides is often the main cause of many vascular remodeling diseases.Vasoactive peptides have the opposite effect.Therefore, the complex network formed between vasoactive peptides was studied, and the regulation mechanism of the network on vascular function was clarified.It will be helpful to understand the physiological function of vasoactive peptide system and the pathophysiological significance in the occurrence and development of cardiovascular disease.In this study, the effects of Ang II on the release of ET-1 Ang II and ADM from VSMC were observed.The effects of transcriptional activator protein-1 (AP-1) and janus protein tyrosine kinase-signal transducers and activators of transcription pathway1 (Janus) on the activation of vasoactive peptide gene, AP-1 and signal transduction were studied.The relationship between 5(signal transducers and activators of transcription 5 and STAT5 in the regulation of gene transcription.The aim of this study was to reveal the molecular mechanism of Ang II on the relative level regulation of four vasoactive peptides.1 expression and Regulation of vasomotor Peptide in Vascular smooth muscle cells; Gene sequence analysis showed that AP-1 binding sites were found in the promoter region of Ang IIET-1 and ADM genes.The expression of these four vasoactive peptides also depends on the activation of AP-1.The relationship between the DNA binding activity of AP-1 and the expression and dynamic equilibrium of four vasoactive peptides and the position of VSMC in the network equilibrium were investigated, and the molecular mechanism of the relative horizontal regulation of Ang II on the four vasoactive peptides was revealed.The results are as follows:
【学位授予单位】：河北医科大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R543;Q593.3

【引证文献】