G6PD deficiency is implicated in Circle of Willis variants in stroke patients and impairs brain vasculature in...

Area of Science:

• Biochemistry
• Genetics
• Neuroscience

Background:

• Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common hereditary enzyme defect globally.
• Clinical research suggests a potential link between G6PD deficiency and cerebrovascular abnormalities.
• The precise mechanisms by which G6PD deficiency affects cerebral vasculature remain unclear.

Purpose of the Study:

• To investigate the role of Glucose-6-phosphate dehydrogenase (G6PD) in brain vasculature.
• To determine the association between G6PD deficiency and cerebrovascular morphology.
• To elucidate the impact of G6PD deficiency on cerebrovascular angiogenesis.

Main Methods:

• Analysis of cerebrovascular imaging data from stroke patients with G6PD deficiency.
• Pharmacological inhibition of G6PD activity in zebrafish embryos.
• Generation of CRISPR/Cas9-mediated g6pd knockout zebrafish models (homozygous and endothelial cell-specific).
• Transcriptomic data analysis and in vitro experiments.

Main Results:

• Patients with G6PD deficiency showed increased morphological variability in the circle of Willis (CoW), including reduced anterior communicating artery and bilateral A1 segments, and increased fetal posterior cerebral artery (fPCA) incidence.
• G6PD-deficient zebrafish models exhibited cerebrovascular morphological abnormalities and impaired angiogenesis.
• G6PD deficiency resulted in dysfunctional angiogenic responses and induced apoptosis, as evidenced by transcriptomic and in vitro data.

Conclusions:

• G6PD deficiency is associated with Circle of Willis (CoW) variants in stroke patients.
• G6PD deficiency impairs cerebrovascular morphology and angiogenesis.
• This study provides novel insights into the role of G6PD in brain vasculature development and disease.