Metalloproteinase‐dependent cleavage of neuregulin and autocrine stimulation of vascular endothelial cells

Kalinowski, April; Plowes, Nicola J. R.; Huang, Qunhua; Berdejo-Izquierdo, Carla; Russell, Raymond R.; Russell, Kerry S.

doi:10.1096/fj.08-129072

Cited by 44 publications

(31 citation statements)

References 34 publications

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“…Regulated cleavage and release of transmembrane growth factors have been recognized as a common and important mechanism for autocrine and paracrine signaling. Kalinowski et al reported that pro-forms of NRG-1 can be cleaved by TNF converting enzyme in response to the inflammatory cytokines IL-6 and IFN (18). Lemmens et al reported that mechanical strain increases endothelial NRG-1 synthesis and release, but angiotensin II and adrenergic agonists decrease endothelial NRG-1 synthesis and release (1,19).…”

Section: Discussionmentioning

confidence: 99%

Expression and secretion of neuregulin-1 in cardiac microvascular endothelial cells treated with angiogenic factors

Gui

et al. 2018

Exp Ther Med

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Abstract. Neuregulin-1 (NRG-1) is a positive regulator of angiogenesis, which suggests there may be an association between NRG-1 and angiogenic factors. The aim of the present study was to investigate the effect of treating human cardiac microvascular endothelial cells (HCMECs) with angiogenic factors on NRG-1 expression and secretion. HCMECs were cultured and stimulated with vascular endothelial growth factor (VEGF; 100 ng/ml), angiopoietin (Ang)-1 (100 ng/ml) or Ang-2 (100 ng/ml) under normal or hypoxia/serum deprivation (Hypo/SD) conditions for 24 h. The expression of ErbB receptors and NRG-1 in HCMECs was measured by western blot analysis and the secretion of NRG-1 in HCMECs was determined by ELISA. The results demonstrated that ErbB2, ErbB3 and ErbB4 were expressed in HCMECs and that ErbB2 expression levels were notably higher than those of ErbB3 and ErbB4. Under normal culture conditions the expression and secretion of NRG

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Section: Discussionmentioning

confidence: 99%

Expression and secretion of neuregulin-1 in cardiac microvascular endothelial cells treated with angiogenic factors

Gui

et al. 2018

Exp Ther Med

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“…This possible effect of NRG1 on cardiac fibroblasts may involve complex and currently unknown paracrine and juxtacrine pathways (18,29,65). In addition, it has been proposed that NRG1-administration may regulate angiogenesis, which may in turn contribute to its beneficial effects (34,38,46,75).…”

Section: Potential Effects Of Nrg1 Administration That Do Not Involvementioning

confidence: 99%

The role of neuregulin/ErbB2/ErbB4 signaling in the heart with special focus on effects on cardiomyocyte proliferation

Wadugu

Kühn

2012

American Journal of Physiology-Heart and Circulatory Physiology

114

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Wadugu B, Kühn B. The role of neuregulin/ErbB2/ErbB4 signaling in the heart with special focus on effects on cardiomyocyte proliferation. Am J Physiol Heart Circ Physiol 302: H2139 -H2147, 2012. First published March 16, 2012 doi:10.1152/ajpheart.00063.2012.-The signaling complex consisting of the growth factor neuregulin-1 (NRG1) and its tyrosine kinase receptors ErbB2 and ErbB4 has a critical role in cardiac development and homeostasis of the structure and function of the adult heart. Recent research results suggest that targeting this signaling complex may provide a viable strategy for treating heart failure. Clinical trials are currently evaluating the effectiveness and safety of intravenous administration of recombinant NRG1 formulations in heart failure patients. Endogenous as well as administered NRG1 has multiple possible activities in the adult heart, but how these are related is unknown. It has recently been demonstrated that NRG1 administration can stimulate proliferation of cardiomyocytes, which may contribute to repair failing hearts. This review summarizes the current knowledge of how NRG1 and its receptors control cardiac physiology and biology, with special emphasis on its role in cardiomyocyte proliferation during myocardial growth and regeneration. cardiac repair; cardiac regeneration; cardiomyocyte differentiation THIS ARTICLE is part of a collection on Physiological Basis of Cardiovascular Cell and Gene Therapies. Other articles appearing in this collection, as well as a full archive of all collections, can be found online at http://ajpheart.physiology. org/.

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“…Vascular endothelial cells express ErbB receptors and their ligand NRG1 and respond to neuroregulin by proliferation and angiogenesis. On endothelial cells, NRG1 is cleaved by matrix metalloproteinases and acts in an autocrine manner [25]. …”

Section: Discussionmentioning

confidence: 99%

Gene Expression Profile of Blood Cells for the Prediction of Delayed Cerebral Ischemia after Intracranial Aneurysm Rupture: A Pilot Study in Humans

Baumann

Devaux²,

Audibert

et al. 2013

Cerebrovasc Dis

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Background: Delayed cerebral ischemia (DCI) is a potentially devastating complication after intracranial aneurysm rupture and its mechanisms remain poorly elucidated. Early identification of the patients prone to developing DCI after rupture may represent a major breakthrough in its prevention and treatment. The single gene approach of DCI has demonstrated interest in humans. We hypothesized that whole genome expression profile of blood cells may be useful for better comprehension and prediction of aneurysmal DCI. Methods: Over a 35-month period, 218 patients with aneurysm rupture were included in this study. DCI was defined as the occurrence of a new delayed neurological deficit occurring within 2 weeks after aneurysm rupture with evidence of ischemia either on perfusion-diffusion MRI, CT angiography or CT perfusion imaging, or with cerebral angiography. DCI patients were matched against controls based on 4 out of 5 criteria (age, sex, Fisher grade, aneurysm location and smoking status). Genome-wide expression analysis of blood cells obtained at admission was performed by microarrays. Transcriptomic analysis was performed using long oligonucleotide microarrays representing 25,000 genes. Quantitative PCR: 1 µg of total RNA extracted was reverse-transcribed, and the resulting cDNA was diluted 10-fold before performing quantitative PCR. Microarray data were first analyzed by ‘Significance Analysis of Microarrays' software which includes the Benjamini correction for multiple testing. In a second step, microarray data fold change was compared using a two-tailed, paired t test. Analysis of receiver-operating characteristic (ROC) curves and the area under the ROC curves were used for prediction analysis. Logistic regression models were used to investigate the additive value of multiple biomarkers. Results: A total of 16 patients demonstrated DCI. Significance Analysis of Microarrays software failed to retrieve significant genes, most probably because of the heterogeneity of the patients included in the microarray experiments and the small size of the DCI population sample. Standard two-tailed paired t test and C-statistic revealed significant associations between gene expression and the occurrence of DCI: in particular, the expression of neuroregulin 1 was 1.6-fold upregulated in patients with DCI (p = 0.01) and predicted DCI with an area under the ROC curve of 0.96. Logistic regression analyses revealed a significant association between neuroregulin 1 and DCI (odds ratio 1.46, 95% confidence interval 1.02-2.09, p = 0.02). Conclusions: This pilot study suggests that blood cells may be a reservoir of prognostic biomarkers of DCI in patients with intracranial aneurysm rupture. Despite an evident lack of power, this study elicited neuroregulin 1, a vasoreactivity-, inflammation- and angiogenesis-related gene, as a possible candidate predictor of DCI. Larger cohort studies are needed but genome-wide microarray-based studies are promising research tools for the understanding of DCI after intracranial aneurysm rupture.

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Metalloproteinase‐dependent cleavage of neuregulin and autocrine stimulation of vascular endothelial cells

Cited by 44 publications

References 34 publications

Expression and secretion of neuregulin-1 in cardiac microvascular endothelial cells treated with angiogenic factors

Expression and secretion of neuregulin-1 in cardiac microvascular endothelial cells treated with angiogenic factors

The role of neuregulin/ErbB2/ErbB4 signaling in the heart with special focus on effects on cardiomyocyte proliferation

Gene Expression Profile of Blood Cells for the Prediction of Delayed Cerebral Ischemia after Intracranial Aneurysm Rupture: A Pilot Study in Humans

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