ENDOTHELIN ATTENUATES APOPTOSIS IN HUMAN SMOOTH-MUSCLE CELLS

An imbalance between proliferation and apoptosis is an important causa l factor for disorders involving abnormal cell accumulation. Endotheli n (ET)-1, a 21-amino-acid peptide with mitogenic and vasoconstricting activities, not only acts as a mitogen, but also attenuates paclitaxel -induced apoptosis in smooth muscle cells. In both human pericardial a nd prostatic smooth muscle cells, addition of ET-1 reduced paclitaxel- induced DNA fragmentation and phosphatidylserine on the cell surface, two characteristics of apoptosis. By comparison, angiotensin II, anoth er vasoactive peptide, did not have a significant effect on apoptosis. The effect of ET-1 was dose-dependent with an EC50 of 1 nM. These res ults suggest that ET is a potential survival factor for smooth muscle cells, and that altered activity of the ET system in disease states ha s potential to contribute to aberrant cell growth.