ArticleArteriosclerosis, thrombosis, and vascular biology2021
Nrg1β Released in Remote Ischemic Preconditioning Improves Myocardial Perfusion and Decreases Ischemia/Reperfusion Injury via ErbB2-Mediated Rescue of Endothelial Nitric Oxide Synthase and Abrogation of Trx2 Autophagy.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 17 citations in OpenAlex.
- Programmed Cell Death of Endothelial Cells in Ischemic Heart Disease: Mechanism and Potential Cell and Gene Therapeutic Prospects.Bioengineering (Basel, Switzerland) · 2026Review
- Exploring the Potential Mechanism of Polyethylene Terephthalate Associated Cardiotoxicity through Network Toxicology and Molecular Docking.ACS omega · 2026Article
- Involvement of the thioredoxin system in multiple diseases: A focus on mechanisms of action in autophagy and ferroptosis (Review).Molecular medicine reports · 2026Review
- Neuregulin-1 promotes early regenerative and autophagic responses after ischemic stroke via spatial proteomics.Frontiers in cellular neuroscience · 2026Article
- Redox Regulation of KAntioxidants & redox signaling · 2024Review
- High-density lipoprotein regulates angiogenesis by affecting autophagy via miRNA-181a-5p.Science China. Life sciences · 2024Article
- Decreased expression of ErbB2 on left ventricular epicardial cells in patients with diabetes mellitus.Cellular signalling · 2022Article
- Review
- CXCL10 is a novel anti-angiogenic factor downstream of p53 in cardiomyocytes.Physiological reports · 2022Article
- Neuregulin-1, a potential therapeutic target for cardiac repair.Frontiers in pharmacology · 2022Review
- Nrg1β as a Proangiogenesis Therapy: How Is Nrg1β Therapy Unique From Other Angiogenesis Therapies?Arteriosclerosis, thrombosis, and vascular biology · 2021Article
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4 authors at 1 institution in 1 country.
Funding
Abstract
objectiveRemote ischemic preconditioning (RIPC) is an intervention process where the application of multiple cycles of short ischemia/reperfusion (I/R) in a remote vascular bed provides protection against I/R injury. However, the identity of the specific RIPC factor and the mechanism by which RIPC alleviates I/R injury remains unclear. Here, we have investigated the identity and the mechanism by which the RIPC factor provides protection. APPROACH AND
resultsUsing fluorescent in situ hybridization and immunofluorescence, we found that RIPC induces Nrg1β expression in the endothelial cells, which is secreted into the serum. Whereas, RIPC protected against myocardial apoptosis and infarction, treatment with neutralizing-Nrg1 antibodies abolished the protective effect of RIPC. Further, increased superoxide anion generated in RIPC is required for Nrg1 expression. Improved myocardial perfusion and nitric oxide production were achieved by RIPC as determined by contrast echocardiography and electron spin resonance. However, treatment with neutralizing-Nrg1β antibody abrogated these effects, suggesting Nrg1β is a RIPC factor. ErbB2 (Erb-B2 receptor tyrosine kinase 2) is not expressed in the adult murine cardiomyocytes, but expressed in the endothelial cells of heart which is degraded in I/R. RIPC-induced Nrg1β interacts with endothelial ErbB2 and thereby prevents its degradation. Mitochondrial Trx2 (thioredoxin) is degraded in I/R, but rescue of ErbB2 by Nrg1β prevents Trx-2 degradation that decreased myocardial apoptosis in I/R.
conclusionsNrg1β is a RIPC factor that interacts with endothelial ErbB2 and prevents its degradation, which in turn prevents Trx2 degradation due to phosphorylation and inactivation of ATG5 (autophagy-related 5) by ErbB2. Nrg1β also restored loss of eNOS (endothelial nitric oxide synthase) function in I/R via its interaction with Src.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.