Neuregulin-1 Induces Cardiac Hypertrophy and Impairs Cardiac Performance in Post–Myocardial Infarction Rats

Żurek, Magdalena; Johansson, Edvin; Palmer, M Dean; Albery, Tamsin; Johansson, Karin; Rydén-Markinhutha, Katarina

doi:10.1161/circulationaha.119.044313

Cited by 13 publications

(6 citation statements)

References 5 publications

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“…These changes were due to stronger interactions between ventricular cardiomyocytes (C9), ECs (C14, C16) and fibroblasts (C21, C22) in mutant hearts, when compared to controls ( Suppl Fig 10a) . The mutant-TnT heart was highly enriched for ephrin B (which can influence diastolic function 43 ), and pro-fibrotic periostin, TGFβ signaling, whereas mutant-MyHC showed marked enrichment for pro-hypertrophic 44 neuregulin signaling ( Fig 7b-c ). PDGF and ANGPT signaling were predicted to be stronger in mutant-TnT, whereas VEGF signaling was similar in both mutants ( Fig 7b ).…”

Section: Resultsmentioning

confidence: 99%

Single-nucleus RNA/ATAC-seq in early-stage HCM models predicts SWI/SNF-activation in mutant-myocytes, and allele-specific differences in fibroblasts

Thottakara,

Padmanabhan,

Tanriverdi

et al. 2024

Preprint

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Hypertrophic cardiomyopathy (HCM) is associated with phenotypic variability. To gain insights into transcriptional regulation of cardiac phenotype, single-nucleus linked RNA-/ATAC-seq was performed in 5-week-old control mouse-hearts (WT) and two HCM-models (R92W-TnT, R403Q-MyHC) that exhibit differences in heart size/function and fibrosis; mutant data was compared to WT. Analysis of 23,304 nuclei from mutant hearts, and 17,669 nuclei from WT, revealed similar dysregulation of gene expression, activation of AP-1 TFs (FOS, JUN) and the SWI/SNF complex in both mutant ventricular-myocytes. In contrast, marked differences were observed between mutants, for gene expression/TF enrichment, in fibroblasts, macrophages, endothelial cells. Cellchat predicted activation of pro-hypertrophic IGF-signaling in both mutant ventricular-myocytes, and profibrotic TGF-β-signaling only in mutant-TnT fibroblasts. In summary, our bioinformatics analyses suggest that activation of IGF-signaling, AP-1 TFs and the SWI/SNF chromatin remodeler complex promotes myocyte hypertrophy in early-stage HCM. Selective activation of TGFβ-signaling in mutant-TnT fibroblasts contributes to genotype-specific differences in cardiac fibrosis.

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Section: Resultsmentioning

confidence: 99%

Single-nucleus RNA/ATAC-seq in early-stage HCM models predicts SWI/SNF-activation in mutant-myocytes, and allele-specific differences in fibroblasts

Thottakara,

Padmanabhan,

Tanriverdi

et al. 2024

Preprint

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“…However, NRG1 has also been proposed to induce cardiomyocyte hypertrophy ( De Keulenaer et al, 2019 ). In a cardiac magnetic resonance study, it was shown that rhNRG1-treated rats had significantly increased left ventricular wall thickness after MI and increased plasma N-terminal B-type natriuretic peptide precursor levels in a rhNRG1 dose-dependent manner ( Zurek et al, 2020 ), confirming the detrimental effects of rhNRG1-induced hypertrophy and worsened cardiac function.…”

Section: Nrg1 With Cardiovascular Diseasesmentioning

confidence: 93%

“…Therefore, ErbB2 holds promise as a potential target for clinical intervention in HF by NRG1. However, despite proposed explanations for the improvement in cardiomyocyte structure, contractility and proliferation of NRG1 ( De Keulenaer et al, 2019 ), few studies have reported its effects on cardiac output and overall longitudinal strain, as well as LVEF and LV volume ( Zurek et al, 2020 ), making it difficult to fully explain the benefits of NRG1 on left heart function.…”

Section: Nrg1 With Cardiovascular Diseasesmentioning

confidence: 99%

Neuregulin-1, a potential therapeutic target for cardiac repair

et al. 2022

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NRG1 (Neuregulin-1) is an effective cardiomyocyte proliferator, secreted and released by endothelial vascular cells, and affects the cardiovascular system. It plays a major role in heart growth, proliferation, differentiation, apoptosis, and other cardiovascular processes. Numerous experiments have shown that NRG1 can repair the heart in the pathophysiology of atherosclerosis, myocardial infarction, ischemia reperfusion, heart failure, cardiomyopathy and other cardiovascular diseases. NRG1 can connect related signaling pathways through the NRG1/ErbB pathway, which form signal cascades to improve the myocardial microenvironment, such as regulating cardiac inflammation, oxidative stress, necrotic apoptosis. Here, we summarize recent research advances on the molecular mechanisms of NRG1, elucidate the contribution of NRG1 to cardiovascular disease, discuss therapeutic approaches targeting NRG1 associated with cardiovascular disease, and highlight areas for future research.

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“…Cardiac hypertrophy is an essential milestone of many heart diseases, including hypertension [ 1 ], myocardial infarction (MI) [ 2 ], and aortic stenosis [ 3 , 4 ]. It may be the initial adaptive response to maintaining cardiac function; sustained hypertrophy is often accompanied by maladaptive cardiac remodeling that ultimately leads to heart failure and sudden death [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Noncoding RNAs in Cardiac Hypertrophy and Heart Failure

Fan

Xiang

et al. 2022

Cells

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Heart failure is a major global health concern. Noncoding RNAs (ncRNAs) are involved in physiological processes and in the pathogenesis of various diseases, including heart failure. ncRNAs have emerged as critical components of transcriptional regulatory pathways that govern cardiac development, stress response, signaling, and remodeling in cardiac pathology. Recently, studies of ncRNAs in cardiovascular disease have achieved significant development. Here, we discuss the roles of ncRNAs, including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) that modulate the cardiac hypertrophy and heart failure.

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Neuregulin-1 Induces Cardiac Hypertrophy and Impairs Cardiac Performance in Post–Myocardial Infarction Rats

Cited by 13 publications

References 5 publications

Single-nucleus RNA/ATAC-seq in early-stage HCM models predicts SWI/SNF-activation in mutant-myocytes, and allele-specific differences in fibroblasts

Single-nucleus RNA/ATAC-seq in early-stage HCM models predicts SWI/SNF-activation in mutant-myocytes, and allele-specific differences in fibroblasts

Neuregulin-1, a potential therapeutic target for cardiac repair

Noncoding RNAs in Cardiac Hypertrophy and Heart Failure

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