Nogo-B promotes angiogenesis and improves cardiac repair after myocardial infarction via activating Notch1 signaling
Open accessAbstract
Nogo-B (Reticulon 4B) is reportedly a regulator of angiogenesis during the development and progression of cancer. However, whether Nogo-B regulates angiogenesis and post-myocardial infarction (MI) cardiac repair remains elusive. In the present study, we aimed to explore the role and underlying mechanisms of Nogo-B in cardiac repair during MI. We observed an increased expression level of Nogo-B in the heart of mouse MI models, as well as in isolated cardiac microvascular endothelial cells (CMECs). Moreover, Nogo-B was significantly upregulated in CMECs exposed to oxygen-glucose deprivation (OGD). Nogo-B overexpression in the endothelium via cardiotropic adeno-associated virus serotype 9 (AAV9) with the mouse endothelial-specific promoter Tie2 improved heart function, reduced scar size, and increased angiogenesis. RNA-seq data indicated that Notch signaling is a deregulated pathway in isolated CMECs along the border zone of the infarct with Nogo-B overexpression. Mechanistically, Nogo-B activated Notch1 signaling and upregulated Hes1 in the MI hearts. Inhibition of Notch signaling using a specific siRNA and γ-secretase inhibitor abolished the promotive effects of Nogo-B overexpression on network formation and migration of isolated cardiac microvascular endothelial cells (CMECs). Furthermore, endothelial Notch1 heterozygous deletion inhibited Nogo-B-induced cardioprotection and angiogenesis in the MI model. Collectively, this study demonstrates that Nogo-B is a positive regulator of angiogenesis by activating the Notch signaling pathway, suggesting that Nogo-B is a novel molecular target for ischemic disease.
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BODIPY 493/503 detects lipid droplets consisting of neutral lipids.
“BODIPY 493/503, a dye that detects LDs consisting of neutral lipids34,36”
From INPP5D/SHIP1 regulates endo-lysosomal function and cargo-selective phagocytosis in human microglia (2025) · cites this paper as [34]
The Materials and methods sections on immunohistochemical staining and western blotting describe other stains and antibodies, but do not mention BODIPY 493/503 or lipid-droplet detection. Searches for “BODIPY 493/503 lipid droplets neutral lipids” and “BODIPY” found no passage in our copy addressing the claim; page numbers were not available. (LLM, conf=0.76)
Experimental — accuracy not yet measuredLipid droplet accumulation is considered a marker of inflammation in microglia during aging and Alzheimer's disease.
“the accumulation of which is considered a marker of inflammation in microglia during aging and Alzheimer’s disease32–35”
From INPP5D/SHIP1 regulates endo-lysosomal function and cargo-selective phagocytosis in human microglia (2025) · cites this paper as [34]
The Introduction and Results discuss Nogo-B, cardiac endothelial cells, and repair after myocardial infarction. A search for lipid droplets, microglia, aging, and Alzheimer’s disease found no passage in our copy addressing whether lipid droplet accumulation marks microglial inflammation. (LLM, conf=0.76)
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Spatially Resolved Mapping of Monoacylglycerol Lipase Activity in the Brain
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- Authors
- Zheng, Y., Lin, J., Liu, D., Wan, G., Gu, X., & Ma, J.
- Affiliations
- Shanghai University of Medicine and Health Sciences (CN)
- Shanghai Jiao Tong University (CN)
- Corresponding author
- Ma, Jian
- Venue
- Cell Death & Disease
- Published
- 2022-04-05
- Volume
- 13
- Issue
- 4
- Pages
- 306-306
- ISSN
- 2041-4889 (ISSN-L)
- PMC
- PMC8983727
- OpenAlex
- W4224325360
- Cited by
- 110
- References
- 52
- Citations by year
- 2026: 20 · 2025: 53 · 2024: 21 · 2023: 14 · 2022: 1 · 2021: 1
- FWCI
- 7.27
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Cell Death and Disease (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Shanghai Key Laboratory of Molecular Imaging (18DZ2260400, 81970229, 81700354)
- Ruijin Hospital
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- Nogo-B, angiogenesis, myocardial infarction, cardiac repair, Notch1 signaling, Hes1, cardiac microvascular endothelial cells, oxygen-glucose deprivation, gamma-secretase inhibition, AAV9 gene delivery, ischemic heart disease, endothelial cell migration
- MeSH terms
- Animals, Endothelium, Myocardial Infarction, Neovascularization, Pathologic, Signal Transduction, Endothelial Cells, Mice
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