(American Journal of Pathology. 2001;158:781-782.)
© 2001 American Society for Investigative Pathology
Is Singlet Oxygen Antiatherosclerotic?
Thomas W. Stief
Klinikum der Philipps-Universitat Marburg Marburg, Germany
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
type5
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
1O24,11,12
could be of clinical importance for treatment of atherothrombosis.
References
-
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[Abstract/Free Full Text]
-
Rockson SG, Lorenz DP, Cheong WF, Woodburn KW: Photoangioplasty: an emerging clinical cardiovascular role for photodynamic therapy. Circulation 2000, 102:591-596[Abstract/Free Full Text]
-
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[Medline]
-
Stief TW, Fareed J: The antithrombotic factor singlet oxygen/light (1O2/hv). Cin Appl Thrombosis/Themostasis 2000, 6:22–30
-
Ross R: Atherosclerosis: an inflammatory disease. New Engl J Med 1999, 340:115-126[Free Full Text]
-
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[Abstract/Free Full Text]
-
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[Abstract/Free Full Text]
-
Gurfinkel E: Inflammation, infection, or both in atherosclerosis: the ROXIS trial in perspective. J Infect Dis 2000, 181(suppl 3):S566-S568
-
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[Medline]
-
Furchgott R: Endothelium-dependent relaxation, endothelium-derived relaxing factor and photorelaxation of blood vessels. Semin Perinatol 1991, 15:11-15[Medline]
-
Pauling L: Are recommended daily allowances for vitamin C adequate? Proc Natl Acad Sci USA 1974, 71:4442-4446[Abstract/Free Full Text]
-
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[Abstract/Free Full Text]
