Clinical implication of cardiovascular hormones

我们之前报道过，在体内肌细胞-非肌细胞共培养模型中，非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在心肌肥大体外模型中肌细胞-非肌细胞相互作用中的作用。CT-1是一种新型的白细胞介素-6相关细胞因子，具有引起心肌细胞肥大的能力。我们发现，在共培养过程中，CT-1在肥厚过程中起作用，表明CT-1在心脏肥厚过程中起局部调节作用。BNP是一种主要由心室肌细胞产生的心脏激素。在这项研究中，我们产生了靶向BNP破坏的小鼠（BNP^<-/->小鼠）。我们在BNP^<-/->小鼠脑室观察到多灶性纤维化病变。BNP^<-/->小鼠未见全身性高血压和心室肥厚的迹象。在心室压力过载的情况下，BNP^<-/->小鼠的局灶性纤维化病变的大小和数量增加，而在野生型小鼠中没有发现更多的局部纤维化变化。本研究在体内证实了BNP是一种心肌细胞来源的抗纤维化因子，并为其作为心室重构的局部调节剂的作用提供了证据。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。在这项研究中，我们产生了靶向破坏CNP的小鼠（CNP^<-/->小鼠）。CNP^<-/->小鼠由于软骨内成骨受损而表现出严重的侏儒症。它们都能在围产期存活，但只有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。在生长板软骨细胞中靶向表达CNP可挽救CNP^<-/-> micc骨缺损，延长其存活时间。本研究表明，CNP在体内作为软骨内成骨的局部积极调节因子，并提示其在某些形式的骨骼发育不良中的病理生理和治疗意义。少

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