Distinct effect of hypoxia on endothelial cell proliferation and cycling

Endothelial cells (EC) occupy a strategic location in the vasculature as a barrier between the intravascular compartment and underlying tissues; as such, they are often exposed to stresses, such as decreases in ambient oxygen, diminished metabolic substrate, or changes in temperature, that could affect their ability to divide and proliferate. The present study characterizes cell counts, cell cycle distribution, and bromodeoxyuridine incorporation in pulmonary artery and aortic EC exposed to acute and/or chronic hypoxia and other cellular stresses. During hypoxia, EC division slows but does not arrest; progression through the G1-to-S transition point and/or progression from S to G2/M is altered with an increased percent of EC in S phase. These changes in EC cell cycle distribution with hypoxia are dependent on the origin of the EC as well as the ambient oxygen concentration; moreover, they are distinct from changes observed with elevated temperature or glucose deprivation. and differ from the quiescent pattern induced by serum deprivation or high-density confluence. These findings demonstrate that hypoxia exerts a distinct effect on the cell cycle distribution and proliferation of EC.