Hypoxia-induced vascular remodeling responses in the brain are much more robust than other organs.

Exposure to chronic mild hypoxia (CMH; 8-10% O(2)) promotes a robust vascular remodeling response in the brain resulting in 50% increased vessel density over a period of two weeks. It is currently unknown whether blood vessels in other organs show similar responses. To address this question, mice were exposed to CMH for 4 days and various markers of vascular remodeling were examined in the brain along with heart, skeletal muscle, kidney, and liver. In contrast to brain, where CMH strongly promoted endothelial proliferation, none of the peripheral organs showed this response and in heart and liver, CMH notably reduced endothelial proliferation. While the MECA-32 endothelial activation marker was strongly induced by CMH in brain, in peripheral organs it was constitutively expressed either on a sub-population of vessels (heart and skeletal muscle) or on all vessels (kidney and liver), and notably, CMH did not affect expression. Endothelial expression of the tight junction proteins claudin-5 and ZO-1 were markedly increased on cerebral vessels, but in the peripheral organs examined, CMH either had no effect or reduced ZO-1 expression (liver). Finally, while CMH had no impact on the number of Mac-1 positive macrophages in the brain, heart, or skeletal muscle, this number was markedly decreased in the kidney but increased in the liver. Our findings show that the vascular remodeling responses to CMH are organ-specific, with the brain showing a strong angiogenic response and enhanced tight junction protein expression, but heart, skeletal muscle, kidney, and liver failing to show these responses.