Abstract
The effect of adenosine and/or hypoxic growth conditions on the proliferation of bovine aortic and coronary microvascular endothelial cells was investigated. Endothelial cells growing at standard tissue culture conditions were stimulated to proliferate by the addition of adenosine (final concentrations 0.5 μM and 5.0 μM). Cell counts of adenosine-treated cultures were 18-188% greater for aortic cells and 19-52% greater for microvascular cells than cell counts of nontreated control cells. This response was not dose-dependent within a concentration range of 5 nM and 50 μM. When culture medium conditioned by endothelial cells growing at 2% oxygen was added to endothelial cells growing at standard conditions, cell counts were 19-56% greater than controls with fresh nonconditioned medium. This suggests that hypoxia causes endothelial cells to release a factor(s) into the medium which stimulates cell proliferation. The addition of 10^-5M 8-phenyltheophyl-line eliminated the stimulation of proliferation caused by 5.0 μM adenosine or 2% oxygen in both aortic and microvascular cultures. These results suggest that: (1) hypoxia causes the release of adenosine from the cells, and (2) adenosine mediates its stimulatory effect via an external membrane receptor. When adenosine analogues selective for A1 and A2 adenosine receptors were tested, no selectivity was evident; that is, equivalent stimulation was achieved with either analogue. This finding suggests that the mechanism for adenosine-mediated stimulation of cell proliferation might be independent of cyclic AMP. Alternatively, either type of adenosine receptor might be capable of triggering a response(s) that culminates in cell replication. A three hour pulse of adenosine was sufficient for triggering the stimulatory response supporting the idea that a cascade of responses is necessary. Addition of adenosine at the time of seeding or 24 hours after seeding did not affect the stimulatory response. This last finding indicates that the stimulatory response was not due to the fact that the cells were not attached to the dish at the time of adenosine addition.
Meininger, Cynthia Joanne (1987). Adenosine stimulates the rate of proliferation of aortic and microvascular endothelial cells. Texas A&M University. Texas A&M University. Libraries. Available electronically from
https : / /hdl .handle .net /1969 .1 /DISSERTATIONS -26917.