The angiogenic factor CCN1 promotes adhesion and migration of circulating CD34+ progenitor cells: potential role in angiogenesis and endothelial regeneration
Abstract
Tissue regeneration involves the formation of new blood vessels regulated by angiogenic factors. We reported recently that the expression of the angiogenic factor CCN1 is up-regulated under various pathophysiologic conditions within the cardiovascular system. Because CD34+ progenitor cells participate in cardiovascular tissue regeneration, we investigated whether CCN1—detected for the first time in human plasma—promotes the recruitment of CD34+ progenitor cells to endothelial cells, thereby enhancing endothelial proliferation and neovascularization. In this study, we demonstrated that CCN1 and supernatants from CCN1-stimulated human CD34+ progenitor cells promoted proliferation of endothelial cells and angiogenesis in vitro and in vivo. In addition, CCN1 induced migration and transendothelial migration of CD34+ cells and the release of multiple growth factors, chemokines, and matrix metalloproteinase-9 (MMP-9) from these cells. Moreover, the CCN1-specific integrins αMβ2 and αVβ3 are expressed on CD34+ cells and CCN1 stimulated integrin-dependent signaling. Furthermore, integrin antagonists (RGD-peptides) suppressed both binding of CCN1 to CD34+ cells and CCN1-induced adhesion of CD34+ cells to endothelial cells. These data suggest that CCN1 promotes integrin-dependent recruitment of CD34+ progenitor cells to endothelial cells, which may contribute to paracrine effects on angiogenesis and tissue regeneration.
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CCN1 stimulates integrin-dependent recruitment of CD34+ progenitor cells, enhancing endothelial proliferation and neovascularization.
“Furthermore, CCN1 stimulates the integrin-dependent recruitment of CD34+ progenitor cells, thereby enhancing endothelial proliferation and neovascularization [88].”
From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [88]
Overexpression of CCN1 from an adenoviral vector accelerates re-endothelialization after balloon injury.
“Overexpression of CCN1 from an adenoviral vector accelerates re-endothelialization after balloon injury, possibly because CCN1 can recruit CD34+ endothelial progenitor cells to the endothelial monolayer and promote their differentiation [88,138].”
From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [88]
CCN1 can recruit CD34+ endothelial progenitor cells to the endothelial monolayer and promote their differentiation.
“Overexpression of CCN1 from an adenoviral vector accelerates re-endothelialization after balloon injury, possibly because CCN1 can recruit CD34+ endothelial progenitor cells to the endothelial monolayer and promote their differentiation [88,138].”
From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [88]
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- Authors
- Grote, K., Salguero, G., Ballmaier, M., Dangers, M., Drexler, H., & Schieffer, B.
- Affiliations
- Departments ofCardiology and Angiology,
- Pediatric Hematology, and
- Medizinische Hochschule Hannover (DE)
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2007-08-01
- Volume
- 110
- Issue
- 3
- Pages
- 877-885
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W1984831138
- Cited by
- 117
- References
- 43
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 8 · 2023: 2 · 2022: 6 · 2021: 5 · 2020: 2 · 2019: 9 · 2018: 5 · 2017: 7 · 2016: 6 · 2015: 9 · 2014: 8 · 2013: 10 · 2012: 5
- FWCI
- 2.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connective Tissue Growth Factor Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- CYR61, angiogenesis, CD34+ cells, re-endothelialization, cell adhesion, cell migration, integrins, integrin αvβ3, RGD peptide, MMP-9, endothelial cell proliferation, neovascularization, paracrine signaling, tissue regeneration, circulating progenitor cells
- MeSH terms
- Animals, Antineoplastic Agents, Cardiovascular System, Cell Adhesion, Cells, Cultured, Humans, Oligopeptides, Regeneration, Stem Cells, Signal Transduction, Up-Regulation, Macrophage-1 Antigen, Immediate-Early Proteins, Neovascularization, Physiologic, Antigens, CD34, Paracrine Communication, Matrix Metalloproteinase 9, Intercellular Signaling Peptides and Proteins, Integrin alphaVbeta3, Endothelial Cells, Cell Proliferation, Mice, Cysteine-Rich Protein 61
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