Hypoxia and Matrix Viscoelasticity Sequentially Regulate Endothelial Progenitor Cluster-based Vasculogenesis

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2019 Mar 26

PMID 30906859

Citations 31

Authors

Michael R Blatchley

Franklyn Hall

Songnan Wang

Hawley C Pruitt

Sharon Gerecht

Affiliations

Soon will be listed here.

Abstract

Vascular morphogenesis is the formation of endothelial lumenized networks. Cluster-based vasculogenesis of endothelial progenitor cells (EPCs) has been observed in animal models, but the underlying mechanism is unknown. Here, using O-controllabe hydrogels, we unveil the mechanism by which hypoxia, co-jointly with matrix viscoelasticity, induces EPC vasculogenesis. When EPCs are subjected to a 3D hypoxic gradient ranging from <2 to 5%, they rapidly produce reactive oxygen species that up-regulate proteases, most notably MMP-1, which degrade the surrounding extracellular matrix. EPC clusters form and expand as the matrix degrades. Cell-cell interactions, including those mediated by VE-cadherin, integrin-β2, and ICAM-1, stabilize the clusters. Subsequently, EPC sprouting into the stiffer, intact matrix leads to vascular network formation. In vivo examination further corroborated hypoxia-driven clustering of EPCs. Overall, this is the first description of how hypoxia mediates cluster-based vasculogenesis, advancing our understanding toward regulating vascular development as well as postnatal vasculogenesis in regeneration and tumorigenesis.

Citing Articles

Acute Three-Dimensional Hypoxia Regulates Angiogenesis.

Ntekoumes D, Song J, Liu H, Amelung C, Guan Y, Gerecht S Adv Healthc Mater. 2024; 14(2):e2403860.

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The extracellular matrix mechanics in the vasculature.

Wang D, Brady T, Santhanam L, Gerecht S Nat Cardiovasc Res. 2024; 2(8):718-732.

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Hydrogels with tunable mechanical plasticity regulate endothelial cell outgrowth in vasculogenesis and angiogenesis.

Wei Z, Lei M, Wang Y, Xie Y, Xie X, Lan D Nat Commun. 2023; 14(1):8307.

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References

Davis G, Camarillo C . An alpha 2 beta 1 integrin-dependent pinocytic mechanism involving intracellular vacuole formation and coalescence regulates capillary lumen and tube formation in three-dimensional collagen matrix. Exp Cell Res. 1996; 224(1):39-51. DOI: 10.1006/excr.1996.0109. View

Kusuma S, Peijnenburg E, Patel P, Gerecht S . Low oxygen tension enhances endothelial fate of human pluripotent stem cells. Arterioscler Thromb Vasc Biol. 2014; 34(4):913-20. PMC: 3978126. DOI: 10.1161/ATVBAHA.114.303274. View

Smith Q, Macklin B, Chan X, Jones H, Trempel M, Yoder M . Differential HDAC6 Activity Modulates Ciliogenesis and Subsequent Mechanosensing of Endothelial Cells Derived from Pluripotent Stem Cells. Cell Rep. 2018; 24(4):895-908.e6. DOI: 10.1016/j.celrep.2018.06.083. View

Park K, Gerecht S . Hypoxia-inducible hydrogels. Nat Commun. 2014; 5:4075. PMC: 4161608. DOI: 10.1038/ncomms5075. View

Lawson N, Weinstein B . In vivo imaging of embryonic vascular development using transgenic zebrafish. Dev Biol. 2002; 248(2):307-18. DOI: 10.1006/dbio.2002.0711. View

Paguirigan A, Beebe D . Protocol for the fabrication of enzymatically crosslinked gelatin microchannels for microfluidic cell culture. Nat Protoc. 2007; 2(7):1782-8. DOI: 10.1038/nprot.2007.256. View

Taniyama Y, Griendling K . Reactive oxygen species in the vasculature: molecular and cellular mechanisms. Hypertension. 2003; 42(6):1075-81. DOI: 10.1161/01.HYP.0000100443.09293.4F. View

Rey S, Semenza G . Hypoxia-inducible factor-1-dependent mechanisms of vascularization and vascular remodelling. Cardiovasc Res. 2010; 86(2):236-42. PMC: 2856192. DOI: 10.1093/cvr/cvq045. View

Prokoph S, Chavakis E, Levental K, Zieris A, Freudenberg U, Dimmeler S . Sustained delivery of SDF-1α from heparin-based hydrogels to attract circulating pro-angiogenic cells. Biomaterials. 2012; 33(19):4792-800. DOI: 10.1016/j.biomaterials.2012.03.039. View

10.

Ellertsdottir E, Lenard A, Blum Y, Krudewig A, Herwig L, Affolter M . Vascular morphogenesis in the zebrafish embryo. Dev Biol. 2009; 341(1):56-65. DOI: 10.1016/j.ydbio.2009.10.035. View

11.

Francis S, Goh K, Hodivala-Dilke K, Bader B, Stark M, Davidson D . Central roles of alpha5beta1 integrin and fibronectin in vascular development in mouse embryos and embryoid bodies. Arterioscler Thromb Vasc Biol. 2002; 22(6):927-33. DOI: 10.1161/01.atv.0000016045.93313.f2. View

12.

Drake C, Fleming P . Vasculogenesis in the day 6.5 to 9.5 mouse embryo. Blood. 2000; 95(5):1671-9. View

13.

Ceradini D, Kulkarni A, Callaghan M, Tepper O, Bastidas N, Kleinman M . Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat Med. 2004; 10(8):858-64. DOI: 10.1038/nm1075. View

14.

Gory-Faure S, Prandini M, Pointu H, Roullot V, Pignot-Paintrand I, Vernet M . Role of vascular endothelial-cadherin in vascular morphogenesis. Development. 1999; 126(10):2093-102. DOI: 10.1242/dev.126.10.2093. View

15.

Hirota K, Semenza G . Regulation of angiogenesis by hypoxia-inducible factor 1. Crit Rev Oncol Hematol. 2006; 59(1):15-26. DOI: 10.1016/j.critrevonc.2005.12.003. View

16.

Kamei M, Saunders W, Bayless K, Dye L, Davis G, Weinstein B . Endothelial tubes assemble from intracellular vacuoles in vivo. Nature. 2006; 442(7101):453-6. DOI: 10.1038/nature04923. View

17.

Deem T, Cook-Mills J . Vascular cell adhesion molecule 1 (VCAM-1) activation of endothelial cell matrix metalloproteinases: role of reactive oxygen species. Blood. 2004; 104(8):2385-93. PMC: 2710031. DOI: 10.1182/blood-2004-02-0665. View

18.

Davis G, Stratman A, Sacharidou A, Koh W . Molecular basis for endothelial lumen formation and tubulogenesis during vasculogenesis and angiogenic sprouting. Int Rev Cell Mol Biol. 2011; 288:101-65. PMC: 3891664. DOI: 10.1016/B978-0-12-386041-5.00003-0. View

19.

Dejana E . Endothelial cell-cell junctions: happy together. Nat Rev Mol Cell Biol. 2004; 5(4):261-70. DOI: 10.1038/nrm1357. View

20.

Bayless K, Salazar R, Davis G . RGD-dependent vacuolation and lumen formation observed during endothelial cell morphogenesis in three-dimensional fibrin matrices involves the alpha(v)beta(3) and alpha(5)beta(1) integrins. Am J Pathol. 2000; 156(5):1673-83. PMC: 1876924. DOI: 10.1016/s0002-9440(10)65038-9. View