Local photodynamic action of methylene blue favorably modulates the postinterventional vascular wound healing response.
OBJECTIVE
Photodynamic therapy (PDT), the light activation of photosensitizers to produce free radicals, is known to inhibit experimental intimal hyperplasia (IH). However, its clinical application has been limited by the lack of a suitable approach and a clinically appropriate photosensitizer. The aim of this study was to determine the effectiveness of a clinical approach for PDT, while testing its ability to favorably modulate the vascular wound healing response.


METHODS
Rat carotid arteries were balloon-injured (BI), and for PDT, the arteries were irradiated with thermoneutral laser light (lambda = 660 nm, 100 J/cm(2)) after the photosensitizer methylene blue (MB) was delivered locally. Control rats included BI alone and MB after BI alone. Arteries were analyzed after 2 weeks with morphometric evaluation (n = 6) and in situ hybridization for versican and procollagen type I gene expression (digitized image pixel analyses, n = 3).


RESULTS
No IH developed in PDT-treated arteries (0 +/- 0 mm(2); compared with BI, 0.192 +/- 0.006 mm(2); P <.0001). The diameters remained unchanged (PDT, 0.95 +/- 0.04 mm; BI, 0.94 +/- 0.05 mm; uninjured artery, 0.91 +/- 0.06 mm). Arterial injury resulted in an increase of versican and procollagen type I messenger RNA (mRNA) in the adventitia and neointima. In the repopulating cells of the adventitia after PDT, there was a significant decrease in versican mRNA (% of positive pixels per high-power field: PDT, 1.13% +/- 0.39%; BI, 2.93% +/- 0.61%; P <.02), but not in procollagen type I mRNA.


CONCLUSIONS
The decrease of versican mRNA expression of repopulating cells after PDT reflects favorable healing on a molecular level. Site-specific delivery of MB, a clinically appropriate photosensitizer, followed by PDT represents a suitable method to promote favorable healing after balloon intervention and further supports its role for inhibiting postinterventional restenosis.
Heckenkamp
J
J
Division of Vascular Surgery and Wellman Laboratories of Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
Adili
F
F
Kishimoto
J
J
Koch
M
M
Lamuraglia
G M
GM
D000704:Analysis of Variance; D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects* / Q000473:pathology; D002404:Catheterization / Q000009:adverse effects*; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics; D004547:Elastic Tissue / Q000187:drug effects / Q000473:pathology; D005786:Gene Expression Regulation; D006965:Hyperplasia; D007091:Image Processing, Computer-Assisted; D017403:In Situ Hybridization; D007834:Lasers; D037102:Lectins / Q000235:genetics; D037181:Lectins, C-Type; D008297:Male; D008751:Methylene Blue / Q000627:therapeutic use*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D011347:Procollagen / Q000235:genetics; D011509:Proteoglycans / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology; D053675:Versicans; D014945:Wound Healing
D011508:Chondroitin Sulfate Proteoglycans; D037102:Lectins; D037181:Lectins, C-Type; D017319:Photosensitizing Agents; D011347:Procollagen; D011509:Proteoglycans; D012333:RNA, Messenger; C508324:Vcan protein, rat; D053675:Versicans; D008751:Methylene Blue