Chronic mild hypoxia promotes profound vascular remodeling in spinal cord blood vessels, preferentially in white matter, via an α5β1 integrin-mediated mechanism

Angiogenesis, 2018 · DOI: 10.1007/s10456-017-9593-2 · Published: May 1, 2018

Spinal Cord Injury Cardiovascular Science Physiology

Simple Explanation

Spinal cord injury can cause damage to blood vessels, which worsens the initial injury. This study explores whether mild hypoxia can stimulate blood vessel remodeling in the spinal cord, potentially aiding recovery. The researchers found that mild hypoxia promoted endothelial proliferation, increased vascularity, and upregulated key proteins involved in angiogenesis and vascular integrity, particularly in the white matter of the spinal cord. They also discovered that α5β1 integrin plays a crucial role in this process, as mice lacking this integrin showed reduced vascular remodeling in response to hypoxia, suggesting that targeting this integrin could be a therapeutic strategy.

Study Duration

Up to 7 days

Participants

Wild-type female SJL/J mice or α5-EC-KO and their WT littermate controls

Evidence Level

Not specified

Key Findings

1
Chronic mild hypoxia (CMH) promotes endothelial proliferation and increased vascularity in spinal cord blood vessels through angiogenesis and arteriogenesis.
2
CMH increases vascular expression of fibronectin and endothelial expression of the α5β1 integrin, which plays an important role in endothelial proliferation.
3
CMH upregulates endothelial expression of tight junction proteins claudin-5, ZO-1, and occludin, suggesting improved vascular integrity.

Research Summary

This study investigates the impact of chronic mild hypoxia (CMH) on vascular remodeling in the spinal cord, revealing that CMH promotes endothelial proliferation, angiogenesis, and arteriogenesis. The research highlights the upregulation of fibronectin and α5β1 integrin, along with tight junction proteins, suggesting enhanced vascular integrity. Vascular remodeling was more pronounced in white matter, while astrocyte activation was more evident in gray matter. The study demonstrates that α5β1 integrin plays a crucial role in vascular remodeling, as mice lacking this integrin exhibited attenuated responses to hypoxia, suggesting potential therapeutic strategies targeting this pathway.

Practical Implications

Therapeutic Angiogenesis

Stimulation of the α5β1 integrin or controlled use of mild hypoxia might provide new approaches for promoting angiogenesis and improving vascular integrity in spinal cord blood vessels.

Vascular Integrity Improvement

The upregulation of tight junction proteins (claudin-5, ZO-1, and occludin) suggests potential strategies for improving vascular integrity in the spinal cord, which may be beneficial in SCI.

Targeted Treatment Strategies

Given the differential effects of CMH on white and gray matter, targeted treatments can be developed to address the specific needs of each region in SCI.

Study Limitations

1
The study focuses primarily on mice, and further research is needed to determine the applicability of these findings to humans.
2
The mechanisms underlying the differential vascular remodeling responses in white and gray matter require further investigation.
3
The long-term effects and potential side effects of chronic mild hypoxia on spinal cord function need to be evaluated.

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