Cardiac fibrosis in mice lacking brain natriuretic peptide
Cardiac fibrosis in mice lacking brain natriuretic peptide
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DOI：
10.1073/pnas.070371497
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发表时间：
2000-04-11
影响因子：
11.1
通讯作者：
Nakao, K
中科院分区：
文献类型：
--
作者：
Tamura, N;Ogawa, Y;Nakao, K
心脏纤维化的定义是心脏间质成纤维细胞的增殖和细胞外基质成分的生物合成，是由与各种心血管疾病相关的病理事件引发的重塑过程的结果，导致心肌僵硬异常，最终导致心功能障碍。脑利钠肽(BNP)是一种主要由心室肌细胞产生的心脏激素，在充血性心力衰竭和急性心肌梗死患者血浆中浓度显著升高。然而，其确切的功能意义尚未确定。在本文中，我们报道了靶向干扰BNP的小鼠(NPPB(-/-)小鼠)的产生。我们观察到NPPB(-/-)小鼠脑室的多灶性纤维化病变。在NPPB(-/-)小鼠中没有发现系统性高血压和心室肥厚的迹象。作为对脑室压力超负荷的反应，NPPB(-/-)小鼠的局灶性纤维化病变的大小和数量增加，而野生型仔鼠(NPPB(+/+)小鼠)则没有发现局灶性纤维化改变。本研究证实BNP是体内的一种心肌源性抗纤维化因子，并为其作为心室重构的局部调节因子的作用提供了证据。
Cardiac fibrosis, defined as a proliferation of interstitial fibroblasts and biosynthesis of extracellular matrix components in the ventricles of the heart, is a consequence of remodeling processes initiated by pathologic events associated with a variety of cardiovascular disorders, which leads to abnormal myocardial stiffness and, ultimately, ventricular dysfunction. Brain natriuretic peptide (BNP) is a cardiac hormone produced primarily by ventricular myocytes, and its plasma concentrations are markedly elevated in patients with congestive heart failure and acute myocardial infarction. However, its precise functional significance has been undefined. In this paper, we report the generation of mice with targeted disruption of BNP (Nppb(-/-) mice). We observed multifocal fibrotic lesions in the ventricles from Nppb(-/-) mice. No signs of systemic hypertension and ventricular hypertrophy are noted in Nppb(-/-) mice. In response to ventricular pressure overload, focal fibrotic lesions are increased in size and number in Nppb(-/-) mice, whereas no focal fibrotic changes are found in wild-type littermates (Nppb(+/+) mice). This study establishes BNP as a cardiomyocyte-derived antifibrotic factor in vivo and provides evidence for its role as a local regulator of ventricular remodeling.