Durocher D, Grépin C, Nemer M
Laboratoire de developpement et differenciation cardiaques, Institut de recherches cliniques de Montreal, Quebec, Canada.
Recent Prog Horm Res. 1998;53:7-23; discussion 22-3.
Cardiac growth and contractility is profoundly altered in response to various hormones and neurotransmitters as well as by changes in electrolyte balance, blood volume, and blood pressure. In turn, the endocrine heart contributes to body homeostasis by secreting a number of biologically active peptide hormones that act on several target tissues. Atrial natriuretic peptide (ANP) and B-type natiuretic peptide (BNP) are the major secretory products of the endocrine myocardium. These peptide hormones act on many target organs via guanylate cyclase-linked membrane receptors to produce natriuresis, diuresis, vasodilatation, and hypotension. ANP and BNP receptors are found on most organs involved in cardiovascular homeostasis (e.g., kidney, adrenal, vasculature, brain). They are also present in gonads and in pituitary, where they alter steroidogenesis and pituitary hormone secretion. Not surprisingly, changes in blood pressure, volume, or hormone status influence ANP and BNP expression, which is also altered in almost all diseases that affect cardiac function. Thus, studies of ANP and BNP gene expression are relevant for many clinical settings. Moreover, transcription of the ANP and BNP genes characterizes cardiac cells at very early stages of development and is tightly linked to cardiac growth--be it proliferation, as in the fetal heart, or trophic growth, as in postnatal ventricular hypertrophy. Thus, analysis of the molecular circuitry that controls ANP and BNP expression might shed important insight into the complex regulatory pathways that underlie normal and pathologic heart development. Indeed, over the past few years, we have analysed transcriptional control of the ANP and BNP genes in embryonic and postnatal cardiomyocytes and in cardiomyocytes treated with hormones and neurotransmitters that cause cardiomyocyte hypertrophy. These studies have lead to the identification of distinct cis-acting DNA elements that modulate basal and hormone-stimulated transcription. Most importantly, the work also resulted in the isolation and characterization of cardiac-specific transcription factors that play critical roles for cardiac cell differentiation and survival.
心脏的生长和收缩能力会因各种激素、神经递质以及电解质平衡、血容量和血压的变化而发生深刻改变。反过来，内分泌心脏通过分泌多种作用于多个靶组织的生物活性肽激素，对身体的内环境稳态做出贡献。心房利钠肽（ANP）和B型利钠肽（BNP）是内分泌心肌的主要分泌产物。这些肽激素通过与鸟苷酸环化酶相连的膜受体作用于许多靶器官，从而产生利钠、利尿、血管舒张和低血压作用。ANP和BNP受体存在于参与心血管内环境稳态的大多数器官中（如肾脏、肾上腺、血管系统、脑）。它们也存在于性腺和垂体中，在那里它们会改变类固醇生成和垂体激素分泌。毫不奇怪，血压、血容量或激素状态的变化会影响ANP和BNP的表达，而在几乎所有影响心脏功能的疾病中，这种表达也会发生改变。因此，对ANP和BNP基因表达的研究与许多临床情况相关。此外，ANP和BNP基因的转录在心脏发育的非常早期阶段就可表征心脏细胞，并且与心脏生长紧密相关——无论是胎儿心脏中的增殖，还是出生后心室肥大中的营养性生长。因此，对控制ANP和BNP表达的分子机制进行分析，可能会为正常和病理性心脏发育的复杂调控途径提供重要的见解。事实上，在过去几年中，我们已经分析了胚胎期和出生后心肌细胞以及用导致心肌细胞肥大的激素和神经递质处理过的心肌细胞中ANP和BNP基因的转录调控。这些研究已经鉴定出了调节基础转录和激素刺激转录的不同顺式作用DNA元件。最重要的是，这项工作还导致了对心脏特异性转录因子的分离和表征，这些转录因子对心脏细胞的分化和存活起着关键作用。
