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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

我们曾报道，在体内心肌细胞-非心肌细胞共培养模型中，非心肌细胞分泌的内皮素-1参与了心肌肥厚的过程。在这项研究中，我们研究了CT-1的作用，一种新的白细胞介素-6相关的细胞因子，有能力引起心肌细胞肥大，在心肌细胞-非心肌细胞的相互作用，在体外模型的心脏肥大。我们发现CT-1在共培养的心肌肥厚过程中发挥作用，提示CT-1在心肌肥厚过程中作为局部调节剂发挥作用。在这项研究中，我们产生了具有BNP靶向破坏的小鼠（BNP +/->小鼠）。我们观察到BNP <-/->小鼠心室中的多灶性纤维化病变。在BNP <-/->小鼠中没有注意到全身性高血压和心室肥大的迹象。作为对心室压力超负荷的反应，BNP^<-/->小鼠中的局灶性纤维化病变在大小和数量上增加，而没有纤维化。 ...更多信息在野生型同窝仔中发现局部纤维化变化。本研究证实BNP是一种心肌细胞源性抗纤维化因子，并为它作为心室重构的局部调节剂提供了证据。CNP存在于多种中枢和外周组织中，在那里它作为自分泌和旁分泌调节剂发挥作用。在本研究中，我们产生了具有CNP靶向破坏的小鼠（CNP^-/->小鼠）C3 CNP^-/->小鼠由于软骨内骨化受损而显示出严重的侏儒症。它们在围产期都能存活，但不到一半能在产后发育中存活。骨骼表型在组织学上与软骨发育不全患者相似，软骨发育不全是人类侏儒症最常见的遗传形式。CNP在生长板软骨细胞中的靶向表达可以挽救CNP <-/->小鼠的骨骼缺陷并允许其延长存活。这项研究表明，CNP在体内局部作为软骨内骨化的正调节剂，并表明其在某些形式的骨骼发育不良中的病理生理学和治疗意义。少