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A novel role for platelet secretion in angiogenesis, mediating bone marrow-derived cell mobilization and homing
Open accessAbstract
Angiogenesis alleviates hypoxic stress in ischemic tissues or during tumor progression. In addition to endothelial cell proliferation and migration, the angiogenic process requires bone marrow-derived cell (BMDC) recruitment to sites of neovascularization. However, the mechanism of communication between hypoxic tissues and the BM remains unknown. Using 2 models of hypoxia-induced angiogenesis (ischemic hindlimb surgery and subcutaneous tumor growth), we show that platelet infusion promotes BMDC mobilization into the circulation, BMDC recruitment into growing neovasculature, tumor vascularization, and blood flow restoration in ischemic limbs, whereas platelet depletion inhibits these effects. Thus, platelets are required for BMDC recruitment into ischemia-induced vasculature. Secretion of platelet α-granules, but neither dense granules nor platelet aggregation is crucial for BMDC homing and subsequent angiogenesis, as determined using VAMP-8(-/-), Pearl, and integrin Beta 3(-/-) platelets. Finally, platelets sequester tumor-derived promoters of angiogenesis and BMDC mobilization, which are counterbalanced by the antiangiogenic factor thrombospondin-1. A lack of thrombospondin-1 in platelets leads to an imbalance in proangiogenic and antiangiogenic factors and accelerates tumor growth and vascularization. Our data demonstrate that platelets stimulate BMDC homing in a VAMP-8-dependent manner, revealing a previously unknown role for platelets as key mediators between hypoxic tissues and the bone marrow during angiogenesis.
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“Similarly, platelets stimulate the homing of BMDSCs, facilitating angiogenesis in injured and hypoxic tissues [92].”
From The Pathogenesis of Adenomyosis vis-à-vis Endometriosis (2020) · cites this paper as [92]
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Metadata
- Authors
- Feng, W., Madajka, M., Kerr, B. A., Mahabeleshwar, G. H., Whiteheart, S. W., & Byzova, T. V.
- Affiliations
- Cleveland Clinic (US)
- University of Kentucky (US)
- Corresponding author
- Feng, Weiyi
- Madajka, Maria
- Kerr, Bethany A.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2011-04-07
- Volume
- 117
- Issue
- 14
- Pages
- 3893-3902
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC3083301
- OpenAlex
- W2009195214
- Cited by
- 133
- References
- 50
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 3 · 2023: 10 · 2022: 16 · 2021: 12 · 2020: 5 · 2019: 4 · 2018: 7 · 2017: 14 · 2016: 10 · 2015: 8 · 2014: 11 · 2013: 10 · 2012: 8
- FWCI
- 4.16
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Blood (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL071625., R01HL056652, R01HL091893, T32HL007914, R01HL071625)
- National Cancer Institute (CA126847, R01CA126847)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK060933, DK060933)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
- Health Sciences › Dentistry › Periodontics › Periodontal Regeneration and Treatments
- Keywords
- platelet secretion, angiogenesis, cell homing, hypoxia, ischemia, tumor vascularization, thrombospondin-1, alpha-granules, CD61, platelet depletion, hindlimb ischemia, tumor growth
- MeSH terms
- Animals, Hypoxia, Blood Platelets, Bone Marrow Cells, Cell Movement, Female, Male, Mice, Inbred C57BL, Neoplasms, Neovascularization, Pathologic, Tumor Cells, Cultured, Mice, SCID, Mice, Inbred NOD, Mice, Knockout, Oxidative Stress, Thrombospondin 1, Integrin beta3, Cell Growth Processes, R-SNARE Proteins, Mice, Stem Cell Niche
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