Published online before print December 24, 2007, doi: 10.1161/HYPERTENSIONAHA.107.104364
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(Hypertension. 2008;51:e14.)
© 2008 American Heart Association, Inc.
Letters to the Editor |
Response to Lysyl Oxidase Inhibition Is Responsible for the Vascular Elastic Fiber Phenotype
Inserm, U684, Nancy University, Nancy, France
Centre National de la Recherche Scientifique, UMR7079, Paris 6 University, Paris, France
Inserm, U698, Paris 7 University, Paris, France
Inserm, U684, Nancy, France
Inserm, U652, Paris 5 University, Paris, France
Inserm, U684, Nancy University, Nancy, France
Inserm, U734, Nancy University, Nancy, France
Inserm, U828, Bordeaux 1 University, France
Centre National de la Recherche Scientifique, UMR7190, Paris 6 University, Paris, France
Inserm, U693, Paris 11 University, Paris, France
Inserm, U684, Nancy University, Nancy, France
We thank Weissen-Plenz et al1 for their interesting insight into a role of the proinflammatory cytokine granulocyte macrophage colony-stimulating factor (GM-CSF) in the maturation of vascular elastic fibers.2 This consists, for the most part, of the action of lysyl oxidase. However, the authors suggest that other inflammatory mediators, like GM-CSF, in relation to semicarbazide-sensitive amine oxidase (SSAO), are involved in the remodeling of the extracellular matrix. SSAO, also called vascular adhesion protein-1, metabolizes primary amines to generate the corresponding aldehyde, ammonia, and H2O2. Our results do not support a major role for SSAO in the organization of the elastic network in physiology,3 but it could be argued that SSAO is implicated in vascular inflammation.
Indeed, SSAO mediates leukocyte transmigration via both its enzymatic activity and its adhesion function. Anti-SSAO antibody treatments inhibit the migration of leukocytes from the blood into the vascular tissue. Moreover, the end products generated by SSAO activation may induce the expression of P- and E-selectins through H2O24 in endothelial cells. Thus, H2O2 produced by SSAO could stimulate the expression of GM-CSF, because H2O2 increases GM-CSF expression.5 Conversely, it would be of interest to examine whether GM-CSF could influence the expression and/or the maturation of vascular SSAO and consequently inhibits inflammation. This functional interaction between GM-CSF and SSAO in the context of oxidative stress is highly relevant, because their extracellular matrix targets are potentially common. This research is hampered by an incomplete understanding of mechanisms and a lack of selective pharmacological SSAO inhibitors. Design and biological evaluation of SSAO inhibitors with simultaneous blockade of SSAO and GM-CSF represent a major challenge.
Circulating levels of GM-CSF and/or SSAO are increased in patients with vascular diseases. The hypothesis that SSAO and GM-CSF may be valuable indicators of endothelial dysfunction remains to be tested in humans.
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Acknowledgments |
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Disclosures
None.
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References |
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 Top References |
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1. Weissen-Plenz G, Hoffmeier A, Sindermann JR. Lysyl oxidase inhibition is responsible for the vascular elastic fiber phenotype. Hypertension. 2008; 51: e13.
2. Weissen-Plenz G, Eschert H, Volker W, Sindermann JR, Beissert S, Robenek H, Scheld HH, Breithardt G. Granulocyte macrophage colony-stimulating factor deficiency affects vascular elastin production and integrity of elastic lamellae. J Vasc Res. 2007; 45: 103–110.[Medline] [Order article via Infotrieve]
3. Mercier N, Osborne-Pellegrin M, El Hadri K, Kakou A, Labat C, Loufrani L, Henrion D, Challande P, Jalkanen S, Feve B, Lacolley P. Carotid arterial stiffness, elastic fibre network and vasoreactivity in semicarbazide-sensitive amine-oxidase null mouse. Cardiovasc Res. 2006; 72: 349–357.
4. Jalkanen S, Karikoski M, Mercier N, Koskinen K, Henttinen T, Elima K, Salmivirta K, Salmi M. The oxidase activity of vascular adhesion protein-1 (VAP-1) induces endothelial E- and P-selectins and leukocyte binding. Blood. 2007; 10: 1864–1870.
5. DeYulia GJ, Carcamo JM, Borquez-Ojeda O, Shelton CC, Golde DW. Hydrogen peroxide generated extracellularly by receptor-ligand interaction facilitates cell signaling. Proc Natl Acad Sci U S A. 2005; 102: 5044–5049.
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