Antisense regulation of atrial natriuretic peptide expression

Celik, Selvi; Sadegh, Mardjaneh Karbalaei; Morley, Michael; Roselli, Carolina; Ellinor, Patrick T.; Cappola, Thomas P.; Smith, J. Gustav; Gidlöf, Olof

doi:10.1172/jci.insight.130978

Cited by 18 publications

(10 citation statements)

References 40 publications

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“… 66 , 67 Moreover, Celik et al . 68 reported a cis -acting ANP antisense transcript (ANP-AS), negatively regulating ANP expression in human cardiomyocytes, which was increased in heart tissue of patients with advanced HF. Thus, in HF with elevated ANP-AS and an ANP deficiency, ANP-AS might be a contributing mechanism.…”

Section: Differential Regulation Of Anp and Bnp In Heart Failure And ...mentioning

confidence: 99%

Natriuretic peptide pathways in heart failure: further therapeutic possibilities

Sangaralingham

Kühn

Cannone

et al. 2022

Cardiovascular Research

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The discovery of the heart as an endocrine organ resulted in a remarkable recognition of the natriuretic peptide system (NPS). Specifically, research has established the production of atrial (ANP) and B-type natriuretic peptides (BNP) from the heart, which exert pleiotropic cardiovascular, endocrine, renal, and metabolic actions via the particulate guanylyl cyclase A receptor (GC-A) and the second messenger, cGMP. C-type natriuretic peptide (CNP) is produced in the endothelium and kidney and mediates important protective auto/paracrine actions via GC-B and cGMP. These actions, in part, participate in the efficacy of sacubitril/valsartan in heart failure (HF) due to augmentation of the NPS. Here we will review important insights into the biology of the NPS, the role of precision medicine and focus on the phenotypes of human genetic variants of ANP and BNP in the general population and the relevance to HF. We will also provide an update of the existence of NP deficiency states, including in HF, which provide the rationale for further therapeutics for the NPS. Finally, we will review the field of peptide engineering and the development of novel designer NPs for the treatment of HF. Notably, the recent discovery of a first-in-class small molecule GC-A enhancer, which is orally deliverable, will be highlighted. These innovative designer NPs and small molecule possess enhanced and novel properties for the treatment of HF and cardiovascular diseases.

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Section: Differential Regulation Of Anp and Bnp In Heart Failure And ...mentioning

confidence: 99%

Natriuretic peptide pathways in heart failure: further therapeutic possibilities

Sangaralingham

Kühn

Cannone

et al. 2022

Cardiovascular Research

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“…NPPA-AS1 has been shown to play a role in AF via modulation of atrial contractile genes [ 123 ]. Celik et al [ 164 ] studied the molecular mechanism of this lncRNA in iPSC-derived cardiomyocytes (iPSC-CMs), which contained a mixture of atrial, ventricular, and nodal CMs. They found that NPPA-AS1 was localized to the nucleus in iPSC-CMs.…”

Section: Deciphering Lncrna Function In Atrial Fibrillation By Hpsmentioning

confidence: 99%

Long Non-Coding RNAs in Atrial Fibrillation: Pluripotent Stem Cell-Derived Cardiomyocytes as a Model System

Bektik

Cowan

Wang

2020

IJMS

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Atrial fibrillation (AF) is a type of sustained arrhythmia in humans often characterized by devastating alterations to the cardiac conduction system as well as the structure of the atria. AF can lead to decreased cardiac function, heart failure, and other complications. Long non-coding RNAs (lncRNAs) have been shown to play important roles in the cardiovascular system, including AF; however, a large group of lncRNAs is not conserved between mouse and human. Furthermore, AF has complex networks showing variations in mechanisms in different species, making it challenging to utilize conventional animal models to investigate the functional roles and potential therapeutic benefits of lncRNAs for AF. Fortunately, pluripotent stem cell (PSC)-derived cardiomyocytes (CMs) offer a reliable platform to study lncRNA functions in AF because of certain electrophysiological and molecular similarities with native human CMs. In this review, we first summarize the broad aspects of lncRNAs in various heart disease settings, then focus on their potential roles in AF development and pathophysiology. We also discuss current uses of PSCs in AF research and describe how these studies could be developed into novel therapeutics for AF and other cardiovascular diseases.

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“…In heart failure patients, increased IR of essential cardiac constituents such as Titin, is hypothesized to be involved in the cellular stress response (Boeckel et al, 2021), which would be consistent with our observations. There is also growing evidence that antisense-mediated gene regulation is involved in different pathophysiological contexts, including heart disease (Luther, 2005;Zinad et al, 2017;Celik et al, 2019). Recently, a long non-coding RNA transcribed antisense near the Actc1 gene was described for its role in cardiomyocyte proliferation and cardiac repair (Ponnusamy et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Full-Length Spatial Transcriptomics Reveals the Unexplored Isoform Diversity of the Myocardium Post-MI

Boileau

Vries

et al. 2022

Front. Genet.

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We introduce Single-cell Nanopore Spatial Transcriptomics (scNaST), a software suite to facilitate the analysis of spatial gene expression from second- and third-generation sequencing, allowing to generate a full-length near-single-cell transcriptional landscape of the tissue microenvironment. Taking advantage of the Visium Spatial platform, we adapted a strategy recently developed to assign barcodes to long-read single-cell sequencing data for spatial capture technology. Here, we demonstrate our workflow using four short axis sections of the mouse heart following myocardial infarction. We constructed a de novo transcriptome using long-read data, and successfully assigned 19,794 transcript isoforms in total, including clinically-relevant, but yet uncharacterized modes of transcription, such as intron retention or antisense overlapping transcription. We showed a higher transcriptome complexity in the healthy regions, and identified intron retention as a mode of transcription associated with the infarct area. Our data revealed a clear regional isoform switching among differentially used transcripts for genes involved in cardiac muscle contraction and tissue morphogenesis. Molecular signatures involved in cardiac remodeling integrated with morphological context may support the development of new therapeutics towards the treatment of heart failure and the reduction of cardiac complications.

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Antisense regulation of atrial natriuretic peptide expression

Cited by 18 publications

References 40 publications

Natriuretic peptide pathways in heart failure: further therapeutic possibilities

Natriuretic peptide pathways in heart failure: further therapeutic possibilities

Long Non-Coding RNAs in Atrial Fibrillation: Pluripotent Stem Cell-Derived Cardiomyocytes as a Model System

Full-Length Spatial Transcriptomics Reveals the Unexplored Isoform Diversity of the Myocardium Post-MI

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