Photodynamic therapy mediated induction of accelerated re-endothelialisation following injury to the arterial wall: implications for the prevention of postinterventional restenosis.
OBJECTIVE
Accelerated re-endothelialisation may inhibit the development of restenosis. Basic Fibroblast Growth Factor (bFGF) plays a key role for early proliferative activity in the artery following injury. Therefore, this study was devised to examine the effect of photodynamic therapy (PDT) on post-injury re-endothelialisation in vivo, and bFGF-mRNA expression in endothelial cells (EC) in vitro.


METHODS
Rat carotid arteries were balloon-injured prior to PDT. Arteries were analysed after 1, 3, 5, 14 and 30 days. Morphometric measurements were undertaken following injection of 0.5% Evans Blue which stains non-endothelialised surfaces only. To identify EC, immunohistochemistry (CD-31) was performed. Proliferation was assessed by fluorescence cell counting. PCR quantification of bFGF-mRNA expression and proliferation were assessed in bovine aortic EC which were plated on isolated, PDT-treated EC-derived extracellular matrix at (12), 24, 48 (72 h).


RESULTS
Three days following PDT, arteries displayed significantly increased endothelial lining (p = 0.02), which was more pronounced at 5 (p = 0.03) and 14 days (p = 0.02). At 30 days no relevant differences between PDT and control were noted. EC proliferation on PDT-treated matrix was significantly increased at 24, 48, and 72 h (p = 0.0004), whereas bFGF-mRNA expression was significantly increased at 24 h only (p = 0.007).


CONCLUSIONS
Post-injury PDT appears to accelerate re-endothelialisation. Expression of bFGF-mRNA, however, although increased shortly after PDT, may not be responsible for a constant stimulation of EC proliferation.
Adili
F
F
Division of Vascular and Endovascular Surgery, Johann Wolfgang Goethe-University, Frankfurt, Germany.
Scholz
T
T
Hille
M
M
Heckenkamp
J
J
Barth
S
S
Engert
A
A
Schmitz-Rixen
T
T
D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects / Q000503:physiopathology / Q000528:radiation effects; D020212:Carotid Artery Injuries / Q000503:physiopathology / Q000628:therapy; D023903:Coronary Restenosis / Q000235:genetics / Q000503:physiopathology* / Q000517:prevention & control*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000293:injuries* / Q000503:physiopathology / Q000528:radiation effects*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects* / Q000235:genetics / Q000528:radiation effects*; D066298:In Vitro Techniques; D010778:Photochemotherapy; D012333:RNA, Messenger / Q000187:drug effects* / Q000235:genetics / Q000528:radiation effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects*
D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2