AMBIENT-PRESSURE STIMULATES IMMORTALIZED HUMAN AORTIC ENDOTHELIAL-CELLS TO INCREASE DNA-SYNTHESIS AND MATRIX METALLOPROTEINASE-1 (TISSUE COLLAGENASE) PRODUCTION

In the present study, we investigated the effect of ambient pressure o n [H-3]-thymidine incorporation and on the production of matrix metall oproteinase 1 (tissue collagenase/proMMP-1) using human aortic endothe lial cells immortalized with simian virus 40 (SE-1). Incubation of cel ls at ambient pressures of 50 and 100 mmHg for 24 h slightly increased [H-3]-thymidine incorporation when directly compared with normal cult ure conditions. The amount of [H-3]-thymidine incorporated in SE-1 rea ched a maximum at 150 mmHg, while a further increase in pressure to 20 0 mmHg decreased incorporation. The same ambient pressure slightly sti mulated human aortic intimal smooth muscle cells (SMC) to increase [3H ]-thymidine incorporation but not medial SMC. Immunoblot analysis also showed that ambient pressure, ranging from 50 to 200 mmHg, like 12-O- tetradecanoyl-phorbol-13-acetate stimulated SE-1 to produce proMMP-1, an effect not seen with either intimal or medial SMC. The amount of pr oMMP-1 produced also reached a maximum level at 150 mmHg. We postulate that human endothelial cells are ambient pressure sensitive and that relatively lower ambient pressures play an important role in the growt h of endothelial cells, while higher pressures injure endothelial cell s, resulting in the initiation of atherosclerosis. This cell line may prove useful in the investigation of both the physiological and pathol ogical roles of blood pressure on endothelial cell function.