Published online before print May 6, 2004, doi: 10.1161/01.ATV.0000131265.76828.8a
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© 2004 American Heart Association, Inc.
Vascular Biology |
DC Electric Fields Induce Distinct Preangiogenic Responses in Microvascular and Macrovascular Cells
From the Departments of Biomedical Sciences (H.B., C.D.M., M.Z.) and Ophthalmology (J.V.F.), Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, Scotland, UK.
Correspondence to Dr. M Zhao, Department of Biomedical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, Scotland, UK. E-mail m.zhao{at}abdn.ac.uk
Objective— Electrical stimulation induces significant angiogenesis in vivo. We have shown recently that electrical stimulation induces directional migration, reorientation, and elongation of macrovascular endothelial cells. Because angiogenesis occurs mainly in the microvasculature, we have extended this observation to include human microvascular endothelial cells (HMEC-1s) and compared the responses with that of vascular fibroblasts and smooth muscle cells and human umbilical vein endothelial cells.
Methods and Results— Four types of vascular cells were cultured in electric fields (EFs). Dynamic cell behaviors were recorded and analyzed with an image analyzer. EFs of 150 to 400 mV/mm induced directed migration, reorientation, and elongation of all the vascular cells. HMEC-1s showed the greatest directional migration (migration rate of 11 µm/h and directedness of 0.35 at 200 mV/mm). Most intriguingly, HMEC-1s migrated toward the cathode, whereas the other cell types migrated toward the anode.
Conclusions— Endothelial cells derived from angiogenic microvascular as opposed to nonangiogenic macrovascular tissues were more responsive to electrical stimulation. This intriguing directional selectivity indicates that a DC electrical signal as a directional cue may be able to play a role in the spatial organization of vascular structure.
Electrical stimulation of 150 to 400 mV/mm induces distinctive preangiogenesis responses by directing microvascular endothelial cells to migrate toward the cathode, whereas macrovascular endothelial cells, fibroblasts, and smooth muscle cells migrate to the anode. The cell type–specific responses suggest that electrical stimulation may play a spatial organizing role in angiogenesis.
Key Words: vascular cells • electrical stimulation • angiogenesis • heterogeneity • cell migration • alignment • orientation
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