Atrial natriuretic peptide inhibits angiotensin II‐stimulated proliferation in fetal cardiomyocytes

O’Tierney, Perrie; Chattergoon, Natasha N.; Louey, Samantha; Giraud, G; Thornburg, Kent L.

doi:10.1113/jphysiol.2010.191098

Cited by 35 publications

(37 citation statements)

References 56 publications

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“…When the concentration of natriuretic peptides increases, Npr1 and Npr2 activation and cGMP/PKG signaling overtake the actions of Npr3. The inhibitory role of natriuretic peptides on cardiomyocyte proliferation through a cGMP-mediated pathway is supported by previous work in fetal sheep cardiomyocytes (O'Tierney et al, 2010). In vivo cell typerestricted elimination of Npr3 will help further define its role in cardiomyocyte proliferation by disassociating the cell-specific effects of this receptor (adenylyl cyclase inhibition) from its role as a modulator of systemic natriuretic peptide levels (clearance role).…”

Section: Research Articlementioning

confidence: 54%

Differential activation of natriuretic peptide receptors modulates cardiomyocyte proliferation during development

et al. 2014

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Organ development is a highly regulated process involving the coordinated proliferation and differentiation of diverse cellular populations. The pathways regulating cell proliferation and their effects on organ growth are complex and for many organs incompletely understood. In all vertebrate species, the cardiac natriuretic peptides (ANP and BNP) are produced by cardiomyocytes in the developing heart. However, their role during cardiogenesis is not defined. Using the embryonic zebrafish and neonatal mammalian cardiomyocytes we explored the natriuretic peptide signaling network during myocardial development. We observed that the cardiac natriuretic peptides ANP and BNP and the guanylate cyclase-linked natriuretic peptide receptors Npr1 and Npr2 are functionally redundant during early cardiovascular development. In addition, we demonstrate that low levels of the natriuretic peptides preferentially activate Npr3, a receptor with Gi activator sequences, and increase cardiomyocyte proliferation through inhibition of adenylate cyclase. Conversely, high concentrations of natriuretic peptides reduce cardiomyocyte proliferation through activation of the particulate guanylate cyclase-linked natriuretic peptide receptors Npr1 and Npr2, and activation of protein kinase G. These data link the cardiac natriuretic peptides in a complex hierarchy modulating cardiomyocyte numbers during development through opposing effects on cardiomyocyte proliferation mediated through distinct cyclic nucleotide signaling pathways.

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Section: Research Articlementioning

confidence: 54%

Differential activation of natriuretic peptide receptors modulates cardiomyocyte proliferation during development

et al. 2014

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“…In contrast, addition of human/ porcine ANP to fetal sheep cardiomyocytes was shown to inhibit angiotensin II-induced proliferation (32). These studies indicate that the biological effects of ANP are cell type specific and may depend on the NPR subtypes expressed in a given cell type.…”

Section: C566mentioning

confidence: 81%

“…ANP high expression zones are associated with a low mitotic index in the E11.5 ventricles. Previous studies showed that ANP/cGMP signaling could either increase proliferation or decrease proliferation of embryonic/fetal cardiomyocytes from the avian or ovine heart, respectively (23,32). The effects of ANP on proliferation of either CPCs or cardiomyocytes from earlier developmental stages have not yet been determined.…”

Section: E115 Ventricular Cells and Gets Cleaved Into Its Biologicalmentioning

confidence: 99%

“…Because the adult mammalian heart is considered a postmitotic organ, disturbances to the proliferation kinetics of CPCs or cardiomyocytes during development could have deleterious effects on heart formation and function in postnatal life. Several reports have pointed to the ability of ANP to modulate proliferation of various cardiovascular cell types including cardiac fibroblasts (8), vascular smooth muscle cells (37), mesangial cells (41), and cardiomyocytes from late embryonic/ fetal stages of development (23,32). Importantly, discrepancies regarding the effects of ANP on proliferation of cardiomyocytes have been reported.…”

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confidence: 99%

“…Importantly, discrepancies regarding the effects of ANP on proliferation of cardiomyocytes have been reported. Specifically, exogenous addition of human ANP on embryonic chick cardiomyocytes was shown to increase proliferation (23), while addition of human/ porcine ANP to fetal sheep cardiomyocytes was shown to inhibit angiotensin II-stimulated proliferation (32). Currently, it remains unknown whether ANP has any effect on the cell cycle kinetics of embryonic CPCs.…”

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confidence: 99%

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Atrial natriuretic peptide inhibits cell cycle activity of embryonic cardiac progenitor cells via its NPRA receptor signaling axis

Hotchkiss

Feridooni

Baguma-Nibasheka

et al. 2015

American Journal of Physiology-Cell Physiology

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(NPRs), which can either activate guanylyl cyclase (NPRA and NPRB) or inhibit adenylyl cyclase (NPRC) to modulate intracellular cGMP or cAMP, respectively. During cardiac development, ANP serves as an early maker of differentiating atrial and ventricular chamber myocardium. As development proceeds, expression of ANP persists in the atria but declines in the ventricles. Currently, it is not known whether ANP is secreted or the ANP-NPR signaling system plays any active role in the developing ventricles. Thus the primary aims of this study were to 1) examine biological activity of ANP signaling systems in embryonic ventricular myocardium, and 2) determine whether ANP signaling modulates proliferation/differentiation of undifferentiated cardiac progenitor cells (CPCs) and/or cardiomyocytes. Here, we provide evidence that ANP synthesized in embryonic day (E)11.5 ventricular myocytes is actively secreted and processed to its biologically active form. Notably, NPRA and NPRC were detected in E11.5 ventricles and exogenous ANP stimulated production of cGMP in ventricular cell cultures. Furthermore, we showed that exogenous ANP significantly decreased cell number and DNA synthesis of CPCs but not cardiomyocytes and this effect could be reversed by pretreatment with the NPRA receptorspecific inhibitor A71915. ANP treatment also led to a robust increase in nuclear p27 levels in CPCs compared with cardiomyocytes. Collectively, these data provide evidence that in the developing mammalian ventricles ANP plays a local paracrine role in regulating the balance between CPC proliferation and differentiation via NPRA/ cGMP-mediated signaling pathways. embryonic heart; ANP; natriuretic peptide receptors; gene expression; cardiac progenitor cells; cardiomyocytes; lineage tracking; knockin mice; cell proliferation and differentiation ATRIAL NATRIURETIC PEPTIDE (ANP) is a 28 amino acid peptide that is synthesized and stored primarily in secretory granules of atrial cardiomyocytes in the adult heart. Ligand binding of ANP to its cognate natriuretic peptide receptors (NPRs) can either activate guanylyl cyclase (NPRA and NPRB) or inhibit adenylyl cyclase (NPRC) to modulate intracellular cGMP or cAMP, respectively. The primary stimulus for ANP secretion from atrial cardiomyocytes is mechanical stretch of the atrial wall (15). In addition to mechanical stimuli, several vasoconstrictor peptides including endothelin-1 (ET-1) (36) and angiotensin II (9), as well as a variety of neurohormones, growth factors, and cytokines, have been shown to modulate natriuretic peptide secretion (10). Once in the circulation, ANP acts in a true endocrine fashion by stimulating NPRA receptors in the kidneys, adrenal cortex, and vasculature to regulate fluid homeostasis and maintain blood pressure via diuretic, natriuretic and vasorelaxant effects (29). In the ventricles of the adult heart, the levels of ANP protein are normally ϳ1,000-fold lower than in the atria and secretory granules are rarely observed (31).In contrast to the adult heart, developmental stud...

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How to Build a Healthy Heart from Scratch

Thornburg

Challis

2014

Advances in Experimental Medicine and Biology

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By any of several measures, the health of the American population has been worsening over the last two decades. Obesity, type 2 diabetes and heart failure have risen dramatically. All the while, the average birthweight at all gestational ages has declined. The relationship between robust growth in the womb and lifelong health is now well established. Likewise, babies born at the low end of the birthweight scale are known to have highly elevated risks for ischemic heart disease, hypertension, stroke and metabolic disease. The biological mechanisms by which developmental plasticity becomes a risk for cardiovascular disease are only now being understood. Translating from animal and human studies, low birthweight babies are likely to have endothelial dysfunction, fewer nephrons, fewer pancreatic beta cells, less vascular elastin, fewer cardiomyocytes, increased sympathetic tone and liver-derived dyslipidemias. Only in the past few years, however, has it become known that maternal and placenta phenotypes are associated with adult onset cardiovascular disease. Helsinki Birth Cohort studies have been especially important in the discovery of these relationships. Sudden cardiac death is associated with a thin placenta and heart failure is associated with a small placenta in short mothers. Coronary heart disease is associated with three combinations of maternal-placental phenotypes. Because the diet is important in providing nutrients for the development of the female body before pregnancy and for providing nutrients during pregnancy, there is increasing evidence that the western diet is an underlying cause for the increase in metabolic disease in the American population. A large segment of the American population suffers from high calorie malnutrition. Scientists in this field now have a responsibility to educate the public on the topic of nutrition and health. This chapter honors Lawrence Longo for decades of work in bringing health to pregnant women and their babies.

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Atrial natriuretic peptide inhibits angiotensin II‐stimulated proliferation in fetal cardiomyocytes

Cited by 35 publications

References 56 publications

Differential activation of natriuretic peptide receptors modulates cardiomyocyte proliferation during development

Differential activation of natriuretic peptide receptors modulates cardiomyocyte proliferation during development

Atrial natriuretic peptide inhibits cell cycle activity of embryonic cardiac progenitor cells via its NPRA receptor signaling axis

How to Build a Healthy Heart from Scratch

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