Molecular and Clinical Study of Cardiovascular Hormones

心血管激素的分子和临床研究

基本信息

批准号：
08044272
负责人：
NAKAO Kazuwa
金额：
$ 4.8万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for international Scientific Research
财政年份：
1996
资助国家：
日本
起止时间：
1996 至无数据
项目状态：
已结题

项目摘要

Recent studies have shown that novel' cardiovascular hormones' may be implicated in various cardiovascular disorders such as hypertension and myocardial infarction. To further explore their roles, we studied the natriuretic peptide system, endothelin system, and renin-angiotensin system at the molecular level in clinical and experimental settings, including genetically engineered animal models.Endothelial production of C-type natriuretic peptide (CNP), possessing vasorelaxant and antiproliferative properties, was markedly increased through TGF-BETA activation under coculture with vascular smooth muscle cells (VSVC), and was significantly decreased by vascular endothelial growth factor or insulin. Furthermore, the G1 arrest was induced by adenovirus-mediated CNP gene transfer into VSMC,and CNP induced an antiproliferative homeobox Gax as opposed to the effect of angiotensinII.Thus, these Multiple mediators may be interacting locally in vascular remodeling, being potential targets for ca … More rdiovacular gene therapy. We also showed that transgenic mice overexpressing brain natriuretic peptide(BNP) exhibited significant hypotension with decreased cardiac mass, suggesting its cardioprotective effect. We further revealed that the BNP and ANP genes are organized in tandem in the mouse and humangenomes.We also revealed the presence of short nonfunctional forms of the endothelin-A receptor in various human tissues by alternative RNA splicing, suggesting a regulatory role in its gene expression.Angiotensin II type 2(AT_2) receptor was abundantly expressed in human myometrium and markedly down-regulated during pregnancy, suggesting its role in uterine function. In cultured rat mesangial cells, the AT_2 receptor was markedly induced upon confluency and exerted an antiproliferative effect, counteracting the AT_1 receptor. Lower expression of the AT_2 receptor in genetically hypertensive rat kidneys suggested its implication in pathogenesis of hypertension. Furthermore, in hypertensive transgenic rats overexpressing mouse renin (Ren-2), cardiac secretion of ANP and BNP upon stimulation was attenuated, suggesting its contribution to their cardiovascular complications. Less

最近的研究如何将塔维尔的心血管梗死'tavel's肌肉梗死。血管肌肉细胞（VSVC），并通过血管渗透性因子或胰岛素显着降低。心脏质量，SUGENT是心脏保护作用。在其基因表达中的作用。在人肌层和肌层中，培养基中有大量表达的血管紧张素II（AT_2）受体。 Recep Ottimend Rat肾脏暗示其在高表达小鼠肾脏（REN-2）的转基因大鼠的发病机理中，ANP和BNP的心脏秘密表明其对R心血管的贡献。