October 15, 2020

Brain blood vessel response to hypoxia

The brain’s response to low oxygen — growth and remodeling of blood vessels — involves certain cell types and molecular pathways, Vanderbilt researchers have discovered.

Chronic hypoxia (low oxygen) in the brain promotes neurovascular angiogenesis — growth of new blood vessels — and remodeling, but the cell types and molecular pathways involved are not completely understood. 

Volker Haase, MD, and colleagues used a genetic approach in mice to investigate the roles of genes that respond to low oxygen in NG2 cells, which are an essential component of the cerebral vasculature. 

They report in Acta Physiologica that activation of hypoxia-inducible factor 2 (HIF2) in NG2 cells turns on the expression of pro-angiogenic genes and induces a pronounced expansion and remodeling of the cerebral vasculature. They also characterized the roles of individual HIF-regulating genes and found that erythropoietin (EPO) does not play a significant role in the HIF2-activated response. 

The studies suggest that NG2 cells play a key role in neurovascular hypoxia responses. The findings have implications for understanding normal physiology and neurologic diseases associated with vascular atrophy and loss of NG2 cells.

Haase is supported by the Krick‐Brooks chair in Nephrology at Vanderbilt University and was a VINNOVA Marie Curie fellow.