Submitted to: Circulation
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/12/2003
Publication Date: 12/16/2003
Citation: Abramowitz, J., Dai, C., Hirschi, K., Dmitrieva, R.I., Doris, P.A., Liu, L., Allen, J.C. 2003. Ouabain- and marinobufagenin-induced proliferation of human umbilical vein smooth muscle cells and a rat vascular smooth muscle cell line, A7r5. Circulation. 108(24):3048-3053. Interpretive Summary: Two steroids, ouabain and marinobufagenin, have growth-promoting effects on many cell types, and are known to promote regeneration of heart tissue in dogs. To investigate possible therapeutic aspects of these steroids, we studied these two sodium pump-selective cardiotonic steroids' impact on vascular smooth muscle cells from both human and rat. Both research suggest that with more study, ouabain and marinobufagenin might have therapeutic value in the regeneration of vascular muscle in humans.
Technical Abstract: We studied the growth-promoting effects of 2 sodium pump-selective cardiotonic steroids, ouabain and marinobufagenin, on cultured cells from vascular smooth muscle (VSMCs) from human umbilical vein and a rat VSMC line, A7r5. Both ouabain and marinobufagenin activated proliferation of these cells in a concentration-dependent manner, reflecting the cardiotonic steroid sensitivity of the specific alpha1 subunit contained within each cell source. The observed effective concentration range of both compounds was below that necessary to induce cytoplasmic ion alterations by sodium pump inhibition. These data indicate that the ouabain-activated proliferative effect previously observed in canine VSMCs occurs in other VSMC sources. This growth effect seems to be initiated by drug interaction with the sodium pump, reflected by the affinity of the steroid for the pump, and is independent of altered transmembrane ionic gradients.