Matrix stiffness regulates neovascular homeostasis through autophagy in nude mice

One of the major obstacles to the effective application of vascularized fruit is an insufficient understanding of the relationship between the microenvironment and neovascular homeostasis. The role of extracellular matrix stiffness in regulating the structural and functional stability of neovascular...

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Bibliographic Details
Published in:Journal of cellular physiology 2023-09, Vol.238 (9), p.2135-2146
Main Authors: Wang, Bingqing, Yang, Yuqing, Wang, Yichen, Yang, Yanxin, Li, Yi, Hu, Chenxi, Xue, Changyue
Format: Article
Language:English
Subjects:
Autophagy
Blood vessels
Bone marrow
Cells (biology)
Dextran
Dextrans
Extracellular matrix
Homeostasis
Hydrogels
Microenvironments
Nitric oxide
Nitric-oxide synthase
Osteoprogenitor cells
Progenitor cells
Stiffness
Structural stability
Structure-function relationships
Vascularization
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Summary:One of the major obstacles to the effective application of vascularized fruit is an insufficient understanding of the relationship between the microenvironment and neovascular homeostasis. The role of extracellular matrix stiffness in regulating the structural and functional stability of neovascularization has not yet been elucidated. This study explored the effects of matrix stiffness on neovascular homeostasis in nude mice. Dextran hydrogels with three different stiffnesses were separately combined with mouse bone marrow-derived endothelial progenitor cells (EPCs) and subcutaneously implanted into the backs of nude mice. After 14 days, neovascular homeostasis indicators in the different groups were measured. Cell autophagy levels were evaluated, and inhibitor assays were performed to explore the underlying mechanism. New blood vessels were generated in the three stiffnesses of the EPC-loaded dextran hydrogels 14 days after implantation. The newly formed vessels tended to have better structural stability in softer hydrogels. Endothelial function markers, such as endothelial nitric oxide synthase and E-selectin, were downregulated as the matrix stiffness increased. Furthermore, we found that cell autophagy levels decreased in stiffer matrices, and autophagy inhibition attenuated neovascular homeostasis. A soft matrix is conducive to maintaining neovascular homeostasis through autophagy in nude mice.
ISSN:0021-9541
1097-4652
DOI:10.1002/jcp.31074