Knockdown of natriuretic peptide receptor-A enhances receptor C expression and signalling in vascular smooth muscle cells

Li, Yuan; Madiraju, Padma; Anand‐Srivastava, Madhu B.

doi:10.1093/cvr/cvr319

Cited by 14 publications

(8 citation statements)

References 39 publications

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“…As the mammalian heart is composed of a heterogeneous mixture of different cell types it will be necessary to determine how the endogenous production of cardiac natriuretic peptides and their receptors regulate the proliferation of these distinctive cell types during cardiogenesis in vivo. In addition, it was shown in mammalian smooth muscle cells that knockdown of Npr1 increased the expression of Npr3, which suggests that cellular pathways exist that regulate the coordinated expression of these receptors (Li et al, 2012). We did not see the same coordinated regulation of Npr1 and Npr3 expression in our in vivo zebrafish model system, but we did see potential feedback regulation of nppa/nppb transcription in our targeted knockdown models.…”

Section: Research Articlementioning

confidence: 60%

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: 60%

Differential activation of natriuretic peptide receptors modulates cardiomyocyte proliferation during development

et al. 2014

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“…Li et al. showed that knockdown of NPR-A leads to upregulation of NPR-C mRNA in vascular smooth muscle cells [56] . However, we did not see any changes in NPR-A mRNA levels with and without treatment on ND or HFD.…”

Section: Discussionmentioning

confidence: 99%

Divergent effects of a designer natriuretic peptide CD-NP in the regulation of adipose tissue and metabolism

Glöde

Naumann

Gnad

et al. 2017

Molecular Metabolism

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ObjectiveObesity is defined as an abnormal increase in white adipose tissue (WAT) and is a major risk factor for type 2 diabetes and cardiovascular disease. Brown adipose tissue (BAT) dissipates energy and correlates with leanness. Natriuretic peptides have been shown to be beneficial for brown adipocyte differentiation and browning of WAT.MethodsHere, we investigated the effects of an optimized designer natriuretic peptide (CD-NP) on murine adipose tissues in vitro and in vivo.ResultsIn murine brown and white adipocytes, CD-NP activated cGMP production, promoted adipogenesis, and increased thermogenic markers. Consequently, mice treated for 10 days with CD-NP exhibited increased “browning” of WAT. To study CD-NP effects on diet-induced obesity (DIO), we delivered CD-NP for 12 weeks. Although CD-NP reduced inflammation in WAT, CD-NP treated DIO mice exhibited a significant increase in body mass, worsened glucose tolerance, and hepatic steatosis. Long-term CD-NP treatment resulted in an increased expression of the NP scavenging receptor (NPR-C) and decreased lipolytic activity.ConclusionsNP effects differed depending on the duration of treatment raising questions about the rational of natriuretic peptide treatment in obese patients.

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“…7 ). Dosage of the 8-Br-cGMP was based on studies from other groups 29 , 30 as well as reports which revealed that only a small fraction of exogenously added 8-Br-cGMP is detectable in the cytoplasm 31 . The addition of 8-Br-cGMP at 10 µM and 100 µM significantly increased the gene expression of HCN4 (3.4-fold and 5.3-fold respectively Vs. control, P < 0.005, Fig.…”

Section: Resultsmentioning

confidence: 99%

Characterizing the role of atrial natriuretic peptide signaling in the development of embryonic ventricular conduction system

Govindapillai

Hotchkiss

Baguma-Nibasheka

et al. 2018

Sci Rep

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Patients born with congenital heart defects frequently encounter arrhythmias due to defects in the ventricular conduction system (VCS) development. Although recent studies identified transcriptional networks essential for the heart development, there is scant information on the mechanisms regulating VCS development. Based on the association of atrial natriuretic peptide (ANP) expression with VCS forming regions, it was reasoned that ANP could play a critical role in differentiation of cardiac progenitor cells (CPCs) and cardiomyocytes (CMs) toward a VCS cell lineage. The present study showed that treatment of embryonic ventricular cells with ANP or cell permeable 8-Br-cGMP can induce gene expression of important VCS markers such as hyperpolarization-activated cyclic nucleotide-gated channel-4 (HCN4) and connexin 40 (Cx40). Inhibition of protein kinase G (PKG) via Rp-8-pCPT-cGMPS further confirmed the role of ANP/NPRA/cGMP/PKG pathway in the regulation of HCN4 and Cx40 gene expression. Additional experiments indicated that ANP may regulate VCS marker gene expression by modulating levels of miRNAs that are known to control the stability of transcripts encoding HCN4 and Cx40. Genetic ablation of NPRA revealed significant decreases in VCS marker gene expression and defects in Purkinje fiber arborisation. These results provide mechanistic insights into the role of ANP/NPRA signaling in VCS formation.

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Knockdown of natriuretic peptide receptor-A enhances receptor C expression and signalling in vascular smooth muscle cells

Abstract: These results demonstrate that knockdown of NPR-A up-regulates the expression of NPR-C, Giα proteins, and NPR-C-linked AC signalling and suggests a cross-talk between NPR-A and NPR-C.

Cited by 14 publications

References 39 publications

Differential activation of natriuretic peptide receptors modulates cardiomyocyte proliferation during development

Differential activation of natriuretic peptide receptors modulates cardiomyocyte proliferation during development

Divergent effects of a designer natriuretic peptide CD-NP in the regulation of adipose tissue and metabolism

Characterizing the role of atrial natriuretic peptide signaling in the development of embryonic ventricular conduction system

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