Mechanisms of microvascular wound repair I. Role of mitosis, oxygen tension, and I-kappa B.
To better understand the mechanisms of both normal reendothelialization and neointimal hyperplasia following injury, human dermal microvascular endothelial cells (HDMEC) were isolated from neonatal foreskin and studied in an in vitro model of the microvascular endothelium. In a standard 3-mm wound of nonproliferative HDMEC cultures, reendothelialization was complete at 32 h at a 20.8% (atmospheric) O(2) level. Inhibition of mitosis by mitomycin C did not reduce reendothelialization and both actinomycin D and cycloheximide inhibited repair by 80%. To determine if signals from injured cells communicated with noninjured cells, diffusion of the dye Lucifer Yellow was followed into injured and surrounding noninjured HDMEC. Diffusion was increased into both injured and noninjured cells, indicating a role for gap junctional intercellular communication (GJIC) in HDMEC wound repair. To determine if a more physiologic O(2) tension (5%) also increased vascular repair, reendothelialization at 5% O(2) was compared to 20.8% O(2) (atmospheric) levels and found to be increased by up to 50% at 5% O(2) at 12 and 24 h postinjury. I-kappa B alpha, the inhibitory subunit of NF-kappa B (a transcription factor activated by oxidative stress), was upregulated following wounding. Retroviral transfection of I-kappa B alpha into HDMEC increased the rate of reendothelialization by 35%, supporting an inhibitory role for NF-kappa B in the control of HDMEC migration.
Chaudhuri
Vaishali
V
Program in Epithelial Biology, Department of Dermatology, Stanford University School of Medicine, Stanford, California 94305, USA.
Potts
Brian R
BR
Karasek
Marvin A
MA
D001808:Blood Vessels / Q000187:drug effects / Q000502:physiology*; D002450:Cell Communication / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D020405:Dermis / Q000098:blood supply / Q000166:cytology; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D017629:Gap Junctions / Q000187:drug effects; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism* / Q000494:pharmacology; D012190:Retroviridae; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects
D020672:I-kappa B Proteins; D010100:Oxygen