To the Editor-in-Chief:
Photoangioplasty is a new therapy of atherothrombosis. 1,2 An important mediator in photodynamic treatment (PDT) is singlet oxygen (1O2). This nonradical oxygen derivative is excited, ie, it emits photons (hv) when returning to ground state oxygen. Physiologically, large concentrations of 1O2 are generated by a combined action of NADPH-oxidase and myeloperoxidase, typical enzymes of polymorphonuclear granulocytes (PMN). 3 Minor concentrations of 1O2 are generated by redox-cycling agents of the quinone type such as phylloquinone (vitamin K), ubiquinone, or tetracycline. 4
In the pathogenesis of atherothrombosis the pathological and chronic inflammatory action of phagocytes of the monocyte/macrophage type 5 should be differentiated from the physiological action of PMN: flowing PMN are activated to PMN that roll on the endothelium; once bound to fibrin, deposited on the endothelial layer, the PMN lyse the thrombus. 4 Therefore, PMN activators and inductors of PMN rolling, such as 1O2, 6 might act anti-atherothrombotically. This could be the primary mechanism of anti-atherosclerotic action of certain antibiotics, such as tetracycline or roxithromycin, and not the direct interaction with chlamydia pathogens. 7,8 1O2/hv might also be involved in the mode of action of NO, 9 photons induce relaxation of smooth muscle cells similarly to NO. 10 The quenching of physiological amounts of 1O2 by cholesterol might result in a pathologically decreased anti-atherothrombotic response. 4 In addition, the present hypothesis on 1O2 as anti-atherosclerotic agent might explain the so-called dark phenomenon of photoangioplasty, ie, the sensitizer without illumination also acts anti-atherosclerotically, presumably by induction of redox-cycling.
Consequently, physiological PMN activators and/or generators of 1O2 4,11,12 could be of clinical importance for treatment of atherothrombosis.
References
- 1.LaMuraglia GM, Schiereck J, Heckenkamp J, Nigri G, Waterman P, Leszczynski D, Kossodo S: Photodynamic therapy induces apoptosis in intimal hyperplastic arteries. Am J Pathol 2000, 157:867-875 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Rockson SG, Lorenz DP, Cheong WF, Woodburn KW: Photoangioplasty: an emerging clinical cardiovascular role for photodynamic therapy. Circulation 2000, 102:591-596 [DOI] [PubMed] [Google Scholar]
- 3.Tatsuzawa H, Maruyama T, Hori K, Sano Y, Nakano M: Singlet oxygen ((1)Delta(g)O(2)) as the principle oxidant in myeloperoxidase-mediated bacterial killing in neutrophil phagosome. Biochem Biophys Res Commun 1999, 262:647-650 [DOI] [PubMed] [Google Scholar]
- 4.Stief TW, Fareed J: The antithrombotic factor singlet oxygen/light (1O2/hv). Cin Appl Thrombosis/Themostasis 2000, 6:22–30 [DOI] [PubMed]
- 5.Ross R: Atherosclerosis: an inflammatory disease. New Engl J Med 1999, 340:115-126 [DOI] [PubMed] [Google Scholar]
- 6.Grether-Beck S, Olaizola-Horn S, Schmitt H, Grewe M, Jahnke A, Johnson JP, Briviba K, Sies H, Krutmann J: Activation of transcription factor AP-2 mediates UVA radiation- and singlet oxygen induced expression of the human intercellular adhesion molecule 1 gene. Proc Natl Acad Sci USA 1996, 93:14586-14591 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Thompson RW, Liao S, Curci JA: Therapeutic potential of tetracycline derivatives to suppress the growth of abdominal aortic aneurysms. Adv Dent Res 1998, 12:159-165 [DOI] [PubMed] [Google Scholar]
- 8.Gurfinkel E: Inflammation, infection, or both in atherosclerosis: the ROXIS trial in perspective. J Infect Dis 2000, 181(suppl 3):S566-S568 [DOI] [PubMed] [Google Scholar]
- 9.Noronha-Dutra AA, Epperlein MM, Woold N: Reaction of nitric oxide with hydrogen peroxide to produce potentially cytotoxic singlet oxygen as a model for nitric oxide-mediated killing. FEBS Lett 1993, 321:59-62 [DOI] [PubMed] [Google Scholar]
- 10.Furchgott R: Endothelium-dependent relaxation, endothelium-derived relaxing factor and photorelaxation of blood vessels. Semin Perinatol 1991, 15:11-15 [PubMed] [Google Scholar]
- 11.Pauling L: Are recommended daily allowances for vitamin C adequate? Proc Natl Acad Sci USA 1974, 71:4442-4446 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Scarpa M, Stevanato R, Viglino P, Rigo A: Superoxide ion as active intermediate in the autoxidation of ascorbate by molecular oxygen: effect of superoxide dismutase. J Biol Chem 1983, 258:6695-6697 [PubMed] [Google Scholar]