Cardiac‑specific deletion of natriuretic peptide receptor A induces differential myocardial expression of circular RNA and mRNA molecules involved in metabolism in mice

Abstract

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are important biological markers and regulators of cardiac function. The natriuretic peptide receptor A (NPRA), also known as NPR1 or guanylyl cyclase A, binds ANP and BNP to initiate transmembrane signal transduction by elevating the intracellular levels of cyclic guanosine monophosphate. However, the effects and mechanisms downstream of NPRA are largely unknown. The aim of the present study was to evaluate the changes in the global pattern of mRNA and circular RNA (circRNA) expression in NPRA −/− and NPRA +/+ myocardium. Differentially expressed mRNA molecules were characterised using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis and were found to be primarily related to metabolic processes. Moreover, circRNA expression was also examined, and a possible competing endogenous RNA network consisting of circRNA, microRNA (miRNA), and mRNA molecules was constructed. The results of this study indicated that NPRA may play a role in cardiac metabolism, which could be mediated by circRNA through endogenous competition mechanisms. These findings may provide insight into future characterisation of various ceRNA network pathways.

Integrative Proteomic and Metabolomic Analysis Reveals Metabolic Phenotype in Mice With Cardiac-Specific Deletion of Natriuretic Peptide Receptor A

“…It is reported that NPRA-deficient mice have low mRNA and protein expression (17,18). Our previous study (9) aslo confirmed that the expression in mRNA and protein of NPRA decreased in the cardiac tissues of the mice.…”

“…All experimental protocols included in this manuscript were approved by the local animal care committee. In the previous research of the group, we have obtained myocardial-specific NPRA knockout mice (9). So we used the mice with cardiomyocyte-specific deletion of NPRA (NPRA flox/flox : Myh6-Cre mice) as in the previous study.…”

The landscape of N6-methyladenosine modification patterns and altered transcript profiles in the cardiac-specific deletion of natriuretic peptide receptor A

“…In our research, the methodology of CRISPR/Case 9 to generate the gene-ablated mice and the NPRA deletion figure were published previously. 27…”

“…And the mice with genotype NprA flox/flox could also be used as control mice (NPRA +/+ ). 27 To achieve tissue-specific deletion of the NPRA gene, NprA flox mice were crossed with CKMM-Cre transgenic mice (Shanghai Model Organisms Center, Inc.) to obtain NprA flox/flox /CKMM-Cre mice. In NprA flox/flox /CKMM-Cre mice, the NPRA gene was specifically disrupted in the myocardium.…”

“…Our previous result showed that there are greatly altered expression profiles in the myocardium tested by RNA-seq 27 and greatly altered metabolic patterns in mice with cardiac-specific deletion of NPRA such as COX, ATP5J2 (mitochondrial membrane ATP synthase), PCr, 2-keto-glutaramic acid (α-KG), etc. 28 Besides, distinguished altered metabolites were also found in HF patients with a remarkably lower cGMP/BNP ratio.…”