title: Human umbilical vein and dermal microvascular endothelial cells show heterogeneity in response to PKC activation.
abstract: Changes in endothelial cell (EC) phenotype are central to the function of endothelium in inflammation. Although these events mainly occur in the microvasculature, previous studies have predominantly used large-vessel EC. Using enzyme-linked immunosorbent and flow cytometric assays, we compared the responses of human umbilical vein endothelial cells (HUVEC) and dermal microvascular endothelial cells (DMEC) to the activation of protein kinase C (PKC). Stimulation with phorbol 12,13-dibutyrate and more selective PKC agonists, including 12-deoxyphorbol 13-phenylacetate 20-acetate (dPPA), induced morphological changes and proliferation in both EC types. PKC activation induced a marked increase in Thy-1 expression on DMEC and only a moderate rise on HUVEC. Furthermore, heterogeneity in the induction of the adhesion molecules intercellular adhesion molecule 1, vascular cell adhesion molecule 1 IVCAM-1), and E-selectin between the two EC types following activation of PKC was demonstrated. In particular, E-selectin and VCAM-1 were significantly upregulated on HUVEC but not DMEC. The data indicate that the PKC pathway is unlikely to be important for E-selectin and VCAM-1 expression in the microvasculature but are consistent with a role for PKC in angiogenesis. This diversity in signaling in response to PKC activation may depend on differential utilization of PKC isozymes and may facilitate specialized endothelial responses.
authors.affiliation: Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.
authors.forename: J C
authors.initials: JC
authors.lastname: Mason
authors.forename: H
authors.initials: H
authors.lastname: Yarwood
authors.forename: K
authors.initials: K
authors.lastname: Sugars
authors.forename: D O
authors.initials: DO
authors.lastname: Haskard
mesh_terms: D015815:Cell Adhesion Molecules; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D019040:E-Selectin / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D004789:Enzyme Activation; D006801:Humans; D007700:Kinetics; D008833:Microcirculation; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D012867:Skin / Q000098:blood supply; D018800:Thy-1 Antigens / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
chemical_list: D015815:Cell Adhesion Molecules; D019040:E-Selectin; D010703:Phorbol Esters; D012333:RNA, Messenger; D018800:Thy-1 Antigens; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D015240:Phorbol 12,13-Dibutyrate; C029704:12-deoxyphorbolphenylacetate; D003513:Cycloheximide; D011493:Protein Kinase C