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Homocysteine-induced endothelial dysfunction through mediating endoplasmic reticulum stress
Xiaoxue Zhang1, Shengtao Xiong2,3, Liang Long2
1Department of Clinical Laboratory, Wuhan Fourth Hospital, China.
The Journal of International Medical Research
|August 1, 2026
Summary
Homocysteine causes cerebral microcirculatory disorders by inducing endoplasmic reticulum stress. This process involves glucose-regulated protein 78, impacting endothelial dysfunction in cerebrovascular diseases.
Area of Science:
- Cardiovascular Research
- Neuroscience
- Molecular Biology
Background:
- Endothelial dysfunction is a critical factor in cardiovascular and cerebrovascular diseases.
- Homocysteine is implicated in various pathological processes, including vascular damage.
Purpose of the Study:
- To investigate the effect of homocysteine on endoplasmic reticulum stress in endothelial dysfunction.
- To explore the role of glucose-regulated protein 78 (GRP78) in homocysteine-mediated endothelial dysfunction.
Main Methods:
- Established a hyperhomocysteinemia mouse model for in vivo studies.
- Utilized in vitro endothelial cell cultures to assess homocysteine's impact on endoplasmic reticulum stress.
- Performed bioinformatics analysis and molecular dynamics simulations to study homocysteine-GRP78 interactions.
Main Results:
- Homocysteine increased adhesion molecules (VCAM1, ICAM1) and decreased tight junction protein 1 in brain tissue.
- Inhibition of endoplasmic reticulum stress ameliorated homocysteine-induced endothelial dysfunction.
- Molecular dynamics simulations identified a key interaction between homocysteine and GRP78.
Conclusions:
- Homocysteine contributes to cerebral microcirculatory disorders.
- The mechanism involves homocysteine-induced endoplasmic reticulum stress, mediated by GRP78 protein function.
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