Cited by 110Congenital heart defects researchCardiac Fibrosis and RemodelingAngiogenesis and VEGF in Cancer

Nogo-B promotes angiogenesis and improves cardiac repair after myocardial infarction via activating Notch1 signaling

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Zheng, Yanjun, Lin, Jingrong, Liu, Dingsheng, Wan, Guoqing, Gu, Xuefeng, Ma, Jian·2022·Cell Death & Disease

Abstract

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)

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  • Lipid 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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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)
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
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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