title: Mechanisms of reduced human vascular cell migration after photodynamic therapy.
abstract: Restenosis results from intimal hyperplasia and constrictive remodeling following cardiovascular interventions. Photodynamic therapy (PDT) has been shown to inhibit intimal hyperplasia in vivo by preventing neointimal repopulation of the treated vessel. This study was undertaken in an attempt to further dissect the mechanisms by which PDT acts on secreted and extracellular matrix proteins to inhibit migration of cultured human vascular cells. PDT of three-dimensional collagen gels inhibited invasive human smooth muscle cell (SMC) migration, whereas cell-derived matrix metalloproteinase production remained unaltered. Additionally, PDT generated cross-links in the collagen gels, a result substantiated in an ex vivo model whereby PDT rendered the treated vessels resistant to pepsin digestion and inhibited invasive migration of SMC and fibroblasts. These data support the premise that by inducing matrix protein cross-links, rendering the vessel resistant to degradation, in vivo PDT inhibits repopulation of the vessel and therefore intimal hyperplasia.
authors.affiliation: Wellman Laboratories of Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Waterman
authors.forename: Marcus
authors.initials: M
authors.lastname: Overhaus
authors.forename: Joerg
authors.initials: J
authors.lastname: Heckenkamp
authors.forename: Giuseppe R
authors.initials: GR
authors.lastname: Nigri
authors.forename: Patrick F C
authors.initials: PF
authors.lastname: Fungaloi
authors.forename: Michael E
authors.initials: ME
authors.lastname: Landis
authors.forename: Sylvie C
authors.initials: SC
authors.lastname: Kossodo
authors.forename: Glenn M
authors.initials: GM
authors.lastname: LaMuraglia
mesh_terms: D001808:Blood Vessels / Q000166:cytology* / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D006083:Graft Occlusion, Vascular / Q000517:prevention & control; D006801:Humans; D006965:Hyperplasia; D018462:Photobiology; D010778:Photochemotherapy