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Atorvastatin and Conditioned Media from Atorvastatin-Treated Human Hematopoietic StemProgenitor-Derived Cells Show Proangiogenic Activity In Vitro but Not In Vivo
Joint Authors
Florczyk, Urszula
Józkowicz, Alicja
Dulak, Jozef
Nowak, Witold N.
Nizankowski, Rafal
Taha, Hevidar
Markiewicz, Joanna
Kachamakova-Trojanowska, Neli
Stępniewski, Jacek
Klóska, Damian
Frołow, Marzena
Walter, Zbigniew
Source
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-15, 15 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-07-16
Country of Publication
Egypt
No. of Pages
15
Main Subjects
Abstract EN
Myeloid angiogenic cells (MAC) derive from hematopoietic stem/progenitor cells (HSPCs) that are mobilized from the bone marrow.
They home to sites of neovascularization and contribute to angiogenesis by production of paracrine factors.
The number and function of proangiogenic cells are impaired in patients with diabetes or cardiovascular diseases.
Both conditions can be accompanied by decreased levels of heme oxygenase-1 (HMOX1), cytoprotective, heme-degrading enzyme.
Our study is aimed at investigating whether precursors of myeloid angiogenic cells (PACs) treated with known pharmaceuticals would produce media with better proangiogenic activity in vitro and if such media can be used to stimulate blood vessel growth in vivo.
We used G-CSF-mobilized CD34+ HSPCs, FACS-sorted from healthy donor peripheral blood mononuclear cells (PBMCs).
Sorted cells were predominantly CD133+.
CD34+ cells after six days in culture were stimulated with atorvastatin (AT), acetylsalicylic acid (ASA), sulforaphane (SR), resveratrol (RV), or metformin (Met) for 48 h.
Conditioned media from such cells were then used to stimulate human aortic endothelial cells (HAoECs) to enhance tube-like structure formation in a Matrigel assay.
The only stimulant that enhanced PAC paracrine angiogenic activity was atorvastatin, which also had ability to stabilize endothelial tubes in vitro.
On the other hand, the only one that induced heme oxygenase-1 expression was sulforaphane, a known activator of a HMOX1 inducer—NRF2.
None of the stimulants changed significantly the levels of 30 cytokines and growth factors tested with the multiplex test.
Then, we used atorvastatin-stimulated cells or conditioned media from them in the Matrigel plug in vivo angiogenic assay.
Neither AT alone in control media nor conditioned media nor AT-stimulated cells affected numbers of endothelial cells in the plug or plug’s vascularization.
Concluding, high concentrations of atorvastatin stabilize tubes and enhance the paracrine angiogenic activity of human PAC cells in vitro.
However, the effect was not observed in vivo.
Therefore, the use of conditioned media from atorvastatin-treated PAC is not a promising therapeutic strategy to enhance angiogenesis.
American Psychological Association (APA)
Nowak, Witold N.& Taha, Hevidar& Markiewicz, Joanna& Kachamakova-Trojanowska, Neli& Stępniewski, Jacek& Klóska, Damian…[et al.]. 2019. Atorvastatin and Conditioned Media from Atorvastatin-Treated Human Hematopoietic StemProgenitor-Derived Cells Show Proangiogenic Activity In Vitro but Not In Vivo. Mediators of Inflammation،Vol. 2019, no. 2019, pp.1-15.
https://search.emarefa.net/detail/BIM-1192643
Modern Language Association (MLA)
Nowak, Witold N.…[et al.]. Atorvastatin and Conditioned Media from Atorvastatin-Treated Human Hematopoietic StemProgenitor-Derived Cells Show Proangiogenic Activity In Vitro but Not In Vivo. Mediators of Inflammation No. 2019 (2019), pp.1-15.
https://search.emarefa.net/detail/BIM-1192643
American Medical Association (AMA)
Nowak, Witold N.& Taha, Hevidar& Markiewicz, Joanna& Kachamakova-Trojanowska, Neli& Stępniewski, Jacek& Klóska, Damian…[et al.]. Atorvastatin and Conditioned Media from Atorvastatin-Treated Human Hematopoietic StemProgenitor-Derived Cells Show Proangiogenic Activity In Vitro but Not In Vivo. Mediators of Inflammation. 2019. Vol. 2019, no. 2019, pp.1-15.
https://search.emarefa.net/detail/BIM-1192643
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1192643