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. 2001 Dec;86(6):612–618. doi: 10.1136/heart.86.6.612

Photodynamic therapy: shedding light on restenosis

R Mansfield 1, S Bown 1, J McEwan 1
PMCID: PMC1729997  PMID: 11711449

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Figure 1  .

Figure 1  

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Mechanism of action of photodynamic therapy. Photosensitising agents are activated by light of a specific wavelength. In its excited state the photosensitiser reacts with tissue oxygen to yield various reactive oxidative species, inducing specific cellular and extracellular effects that lead to inhibition of restenosis (see text). The emission of fluorescence as the photosensitiser decays back to its ground state can be used to study the tissue distribution of the sensitiser.

Figure 2  .

Figure 2  

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Photomicrograph (×400 magnification) of haematoxylin and eosin stained sections of pig coronary artery. Histological changes observed three days after photodynamic therapy (PDT) (top) include endothelial denudation and medial smooth muscle cell eradication. The PDT regime involved local light delivery (50 J/cm2 at a wavelength of 635 nm from a copper vapour dye laser), using a modified standard angioplasty catheter 4-6 hours after systemic sensitisation with 5-aminolaevulinic acid (ALA). A normal untreated vessel is shown for comparison (bottom).

Figure 3  .

Figure 3  

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Modification of a standard transparent Asuka angioplasty balloon for endovascular light delivery. A 100 µm laser fibre with a distal diffuser is placed in the guide wire lumen such that the diffuser is located in the balloon segment, allowing circumferential illumination through the entire balloon surface area.

Figure 4  .

Figure 4  

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Photomicrograph (×40 magnification) of elastin van Giessen stained sections of pig circumflex artery 28 days after oversized balloon injury. The balloon injured control artery (top) shows a greater neointimal area and reduced lumen size than the balloon injured artery that received photodynamic therapy (PDT) (bottom). The PDT regimen involved local light delivery (50 J/cm2 at a wavelength of 635 nm from a copper vapour dye laser) using a modified standard angioplasty catheter 4-6 hours after systemic sensitisation with 5-aminolaevulinic acid (ALA).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adili F., Statius van Eps R. G., Karp S. J., Watkins M. T., LaMuraglia G. M. Differential modulation of vascular endothelial and smooth muscle cell function by photodynamic therapy of extracellular matrix: novel insights into radical-mediated prevention of intimal hyperplasia. J Vasc Surg. 1996 Apr;23(4):698–705. doi: 10.1016/s0741-5214(96)80052-8. [DOI] [PubMed] [Google Scholar]
  2. Allison B. A., Crespo M. T., Jain A. K., Richter A. M., Hsiang Y. N., Levy J. G. Delivery of benzoporphyrin derivative, a photosensitizer, into atherosclerotic plaque of Watanabe heritable hyperlipidemic rabbits and balloon-injured New Zealand rabbits. Photochem Photobiol. 1997 May;65(5):877–883. doi: 10.1111/j.1751-1097.1997.tb01938.x. [DOI] [PubMed] [Google Scholar]
  3. Bauters C., Isner J. M. The biology of restenosis. Prog Cardiovasc Dis. 1997 Sep-Oct;40(2):107–116. doi: 10.1016/s0033-0620(97)80003-5. [DOI] [PubMed] [Google Scholar]
  4. Costa M. A., Sabaté M., van der Giessen W. J., Kay I. P., Cervinka P., Ligthart J. M., Serrano P., Coen V. L., Levendag P. C., Serruys P. W. Late coronary occlusion after intracoronary brachytherapy. Circulation. 1999 Aug 24;100(8):789–792. doi: 10.1161/01.cir.100.8.789. [DOI] [PubMed] [Google Scholar]
  5. Dartsch P. C., Ischinger T., Betz E. Responses of cultured smooth muscle cells from human nonatherosclerotic arteries and primary stenosing lesions after photoradiation: implications for photodynamic therapy of vascular stenoses. J Am Coll Cardiol. 1990 Jun;15(7):1545–1550. doi: 10.1016/0735-1097(90)92824-l. [DOI] [PubMed] [Google Scholar]
  6. Davies M. G., Hagen P. O. Pathobiology of intimal hyperplasia. Br J Surg. 1994 Sep;81(9):1254–1269. doi: 10.1002/bjs.1800810904. [DOI] [PubMed] [Google Scholar]
  7. De Scheerder IK, Wang K, Zhou XR, Verbeken E, Keelan MH, Jr, Horn JB, Sahota H, Kipshidze N. Intravascular Low Power Red Laser Light as an Adjunct to Coronary Stent Implantation Evaluated in a Porcine Coronary Model. J Invasive Cardiol. 1998 Jun;10(5):263–268. [PubMed] [Google Scholar]
  8. Dougherty T. J., Gomer C. J., Henderson B. W., Jori G., Kessel D., Korbelik M., Moan J., Peng Q. Photodynamic therapy. J Natl Cancer Inst. 1998 Jun 17;90(12):889–905. doi: 10.1093/jnci/90.12.889. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Eton D., Colburn M. D., Shim V., Panek W., Lee D., Moore W. S., Ahn S. S. Inhibition of intimal hyperplasia by photodynamic therapy using photofrin. J Surg Res. 1992 Dec;53(6):558–562. doi: 10.1016/0022-4804(92)90254-w. [DOI] [PubMed] [Google Scholar]
  10. Gonschior P., Gerheuser F., Fleuchaus M., Huehns T. Y., Goetz A. E., Welsch U., Sroka R., Dellian M., Lehr H. A., Höfling B. Local photodynamic therapy reduces tissue hyperplasia in an experimental restenosis model. Photochem Photobiol. 1996 Nov;64(5):758–763. doi: 10.1111/j.1751-1097.1996.tb01831.x. [DOI] [PubMed] [Google Scholar]
  11. Gonschior P., Pahl C., Huehns T. Y., Gerheuser F., Erdemci A., Larisch K., Dellian M., Deil S., Goetz A. E., Lehr H. A. Comparison of local intravascular drug-delivery catheter systems. Am Heart J. 1995 Dec;130(6):1174–1181. doi: 10.1016/0002-8703(95)90139-6. [DOI] [PubMed] [Google Scholar]
  12. Grant W. E., Buonaccorsi G., Speight P. M., MacRobert A. J., Hopper C., Bown S. G. The effect of photodynamic therapy on the mechanical integrity of normal rabbit carotid arteries. Laryngoscope. 1995 Aug;105(8 Pt 1):867–871. doi: 10.1288/00005537-199508000-00019. [DOI] [PubMed] [Google Scholar]
  13. Grant W. E., Speight P. M., MacRobert A. J., Hopper C., Bown S. G. Photodynamic therapy of normal rat arteries after photosensitisation using disulphonated aluminium phthalocyanine and 5-aminolaevulinic acid. Br J Cancer. 1994 Jul;70(1):72–78. doi: 10.1038/bjc.1994.252. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Granville D. J., Shaw J. R., Leong S., Carthy C. M., Margaron P., Hunt D. W., McManus B. M. Release of cytochrome c, Bax migration, Bid cleavage, and activation of caspases 2, 3, 6, 7, 8, and 9 during endothelial cell apoptosis. Am J Pathol. 1999 Oct;155(4):1021–1025. doi: 10.1016/S0002-9440(10)65202-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hayase M., Woodbum K. W., Perlroth J., Miller R. A., Baumgardner W., Yock P. G., Yeung A. Photoangioplasty with local motexafin lutetium delivery reduces macrophages in a rabbit post-balloon injury model. Cardiovasc Res. 2001 Feb 1;49(2):449–455. doi: 10.1016/s0008-6363(00)00278-9. [DOI] [PubMed] [Google Scholar]
  16. Hayashi J., Saito T., Aizawa K. Change in chemical composition of lipids accumulated in atheromas of rabbits following photodynamic therapy. Lasers Surg Med. 1997;21(3):287–293. doi: 10.1002/(sici)1096-9101(1997)21:3<287::aid-lsm9>3.0.co;2-m. [DOI] [PubMed] [Google Scholar]
  17. Heckenkamp J., Leszczynski D., Schiereck J., Kung J., LaMuraglia G. M. Different effects of photodynamic therapy and gamma-irradiation on vascular smooth muscle cells and matrix : implications for inhibiting restenosis. Arterioscler Thromb Vasc Biol. 1999 Sep;19(9):2154–2161. doi: 10.1161/01.atv.19.9.2154. [DOI] [PubMed] [Google Scholar]
  18. Henderson B. W., Dougherty T. J. How does photodynamic therapy work? Photochem Photobiol. 1992 Jan;55(1):145–157. doi: 10.1111/j.1751-1097.1992.tb04222.x. [DOI] [PubMed] [Google Scholar]
  19. Hsi R. A., Rosenthal D. I., Glatstein E. Photodynamic therapy in the treatment of cancer: current state of the art. Drugs. 1999 May;57(5):725–734. doi: 10.2165/00003495-199957050-00005. [DOI] [PubMed] [Google Scholar]
  20. Hsiang Y. N., Crespo M. T., Machan L. S., Bower R. D., Todd M. E. Photodynamic therapy for atherosclerotic stenoses in Yucatan miniswine. Can J Surg. 1994 Apr;37(2):148–152. [PubMed] [Google Scholar]
  21. Hsiang Y. N., Crespo M. T., Richter A. M., Jain A. K., Fragoso M., Levy J. G. In vitro and in vivo uptake of benzoporphyrin derivative into human and miniswine atherosclerotic plaque. Photochem Photobiol. 1993 Apr;57(4):670–674. doi: 10.1111/j.1751-1097.1993.tb02935.x. [DOI] [PubMed] [Google Scholar]
  22. Jenkins M. P., Buonaccorsi G. A., Mansfield R., Bishop C. C., Bown S. G., McEwan J. R. Reduction in the response to coronary and iliac artery injury with photodynamic therapy using 5-aminolaevulinic acid. Cardiovasc Res. 2000 Jan 14;45(2):478–485. doi: 10.1016/s0008-6363(99)00352-1. [DOI] [PubMed] [Google Scholar]
  23. Jenkins M. P., Buonaccorsi G. A., Raphael M., Nyamekye I., McEwan J. R., Bown S. G., Bishop C. C. Clinical study of adjuvant photodynamic therapy to reduce restenosis following femoral angioplasty. Br J Surg. 1999 Oct;86(10):1258–1263. doi: 10.1046/j.1365-2168.1999.01247.x. [DOI] [PubMed] [Google Scholar]
  24. Jenkins M. P., Buonaccorsi G., MacRobert A., Bishop C. C., Bown S. G., McEwan J. R. Intra-arterial photodynamic therapy using 5-ALA in a swine model. Eur J Vasc Endovasc Surg. 1998 Oct;16(4):284–291. doi: 10.1016/s1078-5884(98)80047-6. [DOI] [PubMed] [Google Scholar]
  25. Kessel D., Sykes E. Porphyrin accumulation by atheromatous plaques of the aorta. Photochem Photobiol. 1984 Jul;40(1):59–61. doi: 10.1111/j.1751-1097.1984.tb04554.x. [DOI] [PubMed] [Google Scholar]
  26. Kuntz R. E., Baim D. S. Prevention of coronary restenosis : the evolving evidence base for radiation therapy. Circulation. 2000 May 9;101(18):2130–2133. doi: 10.1161/01.cir.101.18.2130. [DOI] [PubMed] [Google Scholar]
  27. LaMuraglia G. M., Adili F., Karp S. J., Statius van Eps R. G., Watkins M. T. Photodynamic therapy inactivates extracellular matrix-basic fibroblast growth factor: insights to its effect on the vascular wall. J Vasc Surg. 1997 Aug;26(2):294–301. doi: 10.1016/s0741-5214(97)70192-7. [DOI] [PubMed] [Google Scholar]
  28. LaMuraglia G. M., ChandraSekar N. R., Flotte T. J., Abbott W. M., Michaud N., Hasan T. Photodynamic therapy inhibition of experimental intimal hyperplasia: acute and chronic effects. J Vasc Surg. 1994 Feb;19(2):321–331. doi: 10.1016/s0741-5214(94)70107-5. [DOI] [PubMed] [Google Scholar]
  29. LaMuraglia G. M., Klyachkin M. L., Adili F., Abbott W. M. Photodynamic therapy of vein grafts: suppression of intimal hyperplasia of the vein graft but not the anastomosis. J Vasc Surg. 1995 Jun;21(6):882–890. doi: 10.1016/s0741-5214(95)70215-6. [DOI] [PubMed] [Google Scholar]
  30. LaMuraglia G. M., Schiereck J., Heckenkamp J., Nigri G., Waterman P., Leszczynski D., Kossodo S. Photodynamic therapy induces apoptosis in intimal hyperplastic arteries. Am J Pathol. 2000 Sep;157(3):867–875. doi: 10.1016/S0002-9440(10)64600-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Landzberg B. R., Frishman W. H., Lerrick K. Pathophysiology and pharmacological approaches for prevention of coronary artery restenosis following coronary artery balloon angioplasty and related procedures. Prog Cardiovasc Dis. 1997 Jan-Feb;39(4):361–398. doi: 10.1016/s0033-0620(97)80034-5. [DOI] [PubMed] [Google Scholar]
  32. Litvack F., Grundfest W. S., Forrester J. S., Fishbein M. C., Swan H. J., Corday E., Rider D. M., McDermid I. S., Pacala T. J., Laudenslager J. B. Effects of hematoporphyrin derivative and photodynamic therapy on atherosclerotic rabbits. Am J Cardiol. 1985 Oct 1;56(10):667–671. doi: 10.1016/0002-9149(85)91032-x. [DOI] [PubMed] [Google Scholar]
  33. Neave V., Giannotta S., Hyman S., Schneider J. Hematoporphyrin uptake in atherosclerotic plaques: therapeutic potentials. Neurosurgery. 1988 Sep;23(3):307–312. doi: 10.1227/00006123-198809000-00004. [DOI] [PubMed] [Google Scholar]
  34. Nobuyoshi M., Kimura T., Nosaka H., Mioka S., Ueno K., Yokoi H., Hamasaki N., Horiuchi H., Ohishi H. Restenosis after successful percutaneous transluminal coronary angioplasty: serial angiographic follow-up of 229 patients. J Am Coll Cardiol. 1988 Sep;12(3):616–623. doi: 10.1016/s0735-1097(88)80046-9. [DOI] [PubMed] [Google Scholar]
  35. Nyamekye I., Anglin S., McEwan J., MacRobert A., Bown S., Bishop C. Photodynamic therapy of normal and balloon-injured rat carotid arteries using 5-amino-levulinic acid. Circulation. 1995 Jan 15;91(2):417–425. doi: 10.1161/01.cir.91.2.417. [DOI] [PubMed] [Google Scholar]
  36. Nyamekye I., Buonaccorsi G., McEwan J., MacRobert A., Bown S., Bishop C. Inhibition of intimal hyperplasia in balloon injured arteries with adjunctive phthalocyanine sensitised photodynamic therapy. Eur J Vasc Endovasc Surg. 1996 Jan;11(1):19–28. doi: 10.1016/s1078-5884(96)80130-4. [DOI] [PubMed] [Google Scholar]
  37. Ortu P., LaMuraglia G. M., Roberts W. G., Flotte T. J., Hasan T. Photodynamic therapy of arteries. A novel approach for treatment of experimental intimal hyperplasia. Circulation. 1992 Mar;85(3):1189–1196. doi: 10.1161/01.cir.85.3.1189. [DOI] [PubMed] [Google Scholar]
  38. Overhaus M., Heckenkamp J., Kossodo S., Leszczynski D., LaMuraglia G. M. Photodynamic therapy generates a matrix barrier to invasive vascular cell migration. Circ Res. 2000 Feb 18;86(3):334–340. doi: 10.1161/01.res.86.3.334. [DOI] [PubMed] [Google Scholar]
  39. Rimington C. Porphyrin and haem biosynthesis and its control. Acta Med Scand Suppl. 1966;445:11–24. doi: 10.1111/j.0954-6820.1966.tb02334.x. [DOI] [PubMed] [Google Scholar]
  40. Rockson S. G., Kramer P., Razavi M., Szuba A., Filardo S., Fitzgerald P., Cooke J. P., Yousuf S., DeVault A. R., Renschler M. F. Photoangioplasty for human peripheral atherosclerosis: results of a phase I trial of photodynamic therapy with motexafin lutetium (Antrin). Circulation. 2000 Nov 7;102(19):2322–2324. doi: 10.1161/01.cir.102.19.2322. [DOI] [PubMed] [Google Scholar]
  41. Salerno D. M., Granrud G., Sharkey P., Asinger R., Hodges M. A controlled trial of propafenone for treatment of frequent and repetitive ventricular premature complexes. Am J Cardiol. 1984 Jan 1;53(1):77–83. doi: 10.1016/0002-9149(84)90687-8. [DOI] [PubMed] [Google Scholar]
  42. Serruys P. W., de Jaegere P., Kiemeneij F., Macaya C., Rutsch W., Heyndrickx G., Emanuelsson H., Marco J., Legrand V., Materne P. A comparison of balloon-expandable-stent implantation with balloon angioplasty in patients with coronary artery disease. Benestent Study Group. N Engl J Med. 1994 Aug 25;331(8):489–495. doi: 10.1056/NEJM199408253310801. [DOI] [PubMed] [Google Scholar]
  43. Spears J. R., Serur J., Shropshire D., Paulin S. Fluorescence of experimental atheromatous plaques with hematoporphyrin derivative. J Clin Invest. 1983 Feb;71(2):395–399. doi: 10.1172/JCI110782. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Statius van Eps R. G., Adili F., Watkins M. T., Anderson R. R., LaMuraglia G. M. Photodynamic therapy of extracellular matrix stimulates endothelial cell growth by inactivation of matrix-associated transforming growth factor-beta. Lab Invest. 1997 Feb;76(2):257–266. [PubMed] [Google Scholar]
  45. Statius van Eps R. G., LaMuraglia G. M. Photodynamic therapy inhibits transforming growth factor beta activity associated with vascular smooth muscle cell injury. J Vasc Surg. 1997 Jun;25(6):1044–1053. doi: 10.1016/s0741-5214(97)70128-9. [DOI] [PubMed] [Google Scholar]
  46. Statius van Eps R. G., Mark L. L., Schiereck J., LaMuraglia G. M. Photodynamic therapy inhibits the injury-induced fibrotic response of vascular smooth muscle cells. Eur J Vasc Endovasc Surg. 1999 Nov;18(5):417–423. doi: 10.1053/ejvs.1999.0911. [DOI] [PubMed] [Google Scholar]
  47. Vincent G. M., Fox J., Charlton G., Hill J. S., McClane R., Spikes J. D. Presence of blood significantly decreases transmission of 630 nm laser light. Lasers Surg Med. 1991;11(5):399–403. doi: 10.1002/lsm.1900110503. [DOI] [PubMed] [Google Scholar]
  48. Visonà A., Angelini A., Gobbo S., Bonanome A., Thiene G., Pagnan A., Tonello D., Bonandini E., Jori G. Local photodynamic therapy with Zn(II)-phthalocyanine in an experimental model of intimal hyperplasia. J Photochem Photobiol B. 2000 Sep;57(2-3):94–101. doi: 10.1016/s1011-1344(00)00083-x. [DOI] [PubMed] [Google Scholar]
  49. Webber J., Kessel D., Fromm D. Side effects and photosensitization of human tissues after aminolevulinic acid. J Surg Res. 1997 Feb 15;68(1):31–37. doi: 10.1006/jsre.1997.5004. [DOI] [PubMed] [Google Scholar]

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