Clinical implication of cardiovascular hormones

心血管激素的临床意义

基本信息

批准号：
10307026
负责人：
NAKAO Kazuwa
金额：
$ 24.83万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A).
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

项目摘要

We previously reported that, using in vivo myocytes-nonmyocytes co-culture model, endothelin-1 secreted from nonmyocytes are involved in the process of cardiac hypertrophy. In this study, we examined a role of CT-1, a novel interleukin-6 related cytokine having ability to evoke cardiac cell hypertrophy, in the myocytes-nonmyocytes interaction in an in vitro model of cardiac hypertrophy. We showed that CT-1 plays a role in the hypertrophic process in the co-culture, suggesting a role of CT-1 as a local regulator during cardiac hypertrophy.BNP is a cardiac hormonc produced primarily by ventricular myocytes. In this study, we generated mice with targeted disruption of BNP (BNP^<-/-> mice). We observed multifocal fibrotic lesions in the ventriceles from BNP^<-/-> mice. No signs of systemic hypertension and ventricular hypertrophy are noted in BNP^<-/-> mice. In response to ventricular pressure overload, focal fibrotic lesions are increased in size and number in BNP^<-/-> mice, whereas no f … More ocal fibrotic changes arc found in wild-type littermates. This study establishes BNP as a cardiomyocyte-derived antifibrotic factor in vivo and provides cvidence for its role as a local regulator of ventricular remodeling.CNP occurs in a variety of central and peripheral tissues, where it acts as an autocrine and paracrinre regulator. In this study, we generated mice with targeted disruption of CNP(CNP^<-/-> mice).The CNP^<-/-> mice show severe dwarfism as a result of imparired endochondral ossification. They are all viable perinatally, but less than half can survive during postnatal developmcnt. The skeletal phenotypes are histologically similar to those seen in patients with achondroplasia, the most common genetic form of human dwarfism. Targeted expression of CNP in the growth plate chondrocytes can rescue the skeletal defect of CNP^<-/-> micc and allow their prolonged survival. This study demonstrates that CNP acts locally as a positive regulator of endochondral ossification in vivo and suggests its pathophysiological and therapcutic implication in some forms of skeletal dysplasia. Less

我们以前曾报道过，使用体内肌细胞 - 非甲性细胞共培养模型，内皮素-1从非甲美生细胞分泌的内皮素-1参与心脏肥大的过程。在这项研究中，我们检查了CT-1的作用，CT-1是一种新型的白介素-6相关的细胞因子，具有唤起心脏细胞肥大的能力，在心肌肥大模型中的肌细胞 - 非肿瘤相互作用中。我们表明，CT-1在共培养中的肥大过程中起作用，这表明CT-1在心脏肥大期间作为局部调节剂的作用。BNP是主要由心室心肌细胞产生的心脏马。在这项研究中，我们产生了针对BNP（BNP^< - / - >小鼠）的靶向破坏的小鼠。我们观察到BNP^< - / - >小鼠的心室中的多灶性纤维化病变。 BNP^< - / - >小鼠没有发现全身性高血压和心室肥大的迹象。对心室压力超负荷的反应，BNP^< - / - >小鼠的大小和数量增加了局灶性纤维化病变，而没有f…在野生型窝窝中发现的更多Ocal纤维化变化。这项研究将BNP确定为体内心肌细胞衍生的抗纤维化因子，并为其作为心室重塑的局部调节剂的作用提供了CVIDEIDE.CNP的作用。CNP发生在各种中央和外围组织中，在各种中央和外围组织中，它充当自分泌和paracraclinre调节剂。在这项研究中，我们产生了靶向破坏CNP（CNP^< - / - >小鼠）的小鼠。CNP^< - / - >小鼠由于内侧软骨的骨化而显示出严重的矮人。它们都是可行的，但是在产后发育过程中，少于一半的人可以生存。在组织学上，骨骼表型与在腺炎患者中相似，这是人类矮人最常见的遗传形式。 CNP在生长板软骨细胞中的靶向表达可以挽救CNP^< - / - > MIC的骨骼缺陷，并允许其延长生存率。这项研究表明，CNP在体内局部充当局部骨化骨化的阳性调节剂，并暗示其在某些形式的骨骼发育不良中的病理生理和热影响。较少的