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 tiss ues; as such, they are often exposed to stresses, such as decreases in ambient oxygen, diminished metabolic substrate, or changes in tempera ture, that could affect their ability to divide and proliferate. The p resent study characterizes cell counts, cell cycle distribution, and b romodeoxyuridine incorporation in pulmonary artery and aortic EC expos ed to acute and/or chronic hypoxia and other cellular stresses. During hypoxia, EC division slows but does not arrest; progression through t he G(1)-to-S transition point and/or progression from S to G(2)/M is a ltered with an increased percent of EC in S phase. These changes in EC cell cycle distribution with hypoxia are dependent on the origin of t he EC as well as the ambient oxygen concentration; moreover, they are distinct from changes observed with elevated temperature or glucose de privation and differ from the quiescent pattern induced by serum depri vation or high-density confluence. These findings demonstrate that hyp oxia exerts a distinct effect on the cell cycle distribution and proli feration of EC.