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Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:1929-1930
doi: 10.1161/01.ATV.0000237564.81178.bb
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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:1929.)
© 2006 American Heart Association, Inc.


Editorials

IL-20 and Atherosclerosis

Another Brick In the Wall

Giuseppina Caligiuri; Srini V. Kaveri; Antonino Nicoletti

From INSERM UMRS 681, Université Pierre et Marie Curie Paris 6, Institut de Recherches Biomédicales des Cordeliers, France.

Correspondence to Giuseppina Caligiuri, INSERM UMRS 681, Université Pierre et Marie Curie Paris 6, Institut de Recherches Biomédicales des Cordeliers, 15, rue de l’Ecole de Médecine, 75006 Paris, France. E-mail giuseppina.caligiuri{at}umrs681.jussieu.fr

Achronic inflammatory process, initiated by lipoprotein extravasation and oxidation in the intimal space, builds up atherosclerotic plaques in the arterial wall.

See page 2090

Cytokines are fundamental actors of inflammation as they exert autocrine and paracrine effects and allow intercellular communication between effector and target cells. More than fifty cytokines have been identified by now. Shortly after their discovery, novel and unexpected biological actions of cytokines are brought to light by cross-disciplinary studies.

Thus, the intersection between the cardiovascular and the immunology research fields has prompted an increasing number of studies focusing on the identification of either proatherogenic or antiatherogenic effects of cytokines (please see Tedgui and Mallat 1 for extensive review).

Blumberg et al2 have used a bioinformatics algorithm designed to identify helical cytokines, which has allowed them to discover a novel cytokine, interleukin (IL)-20. The authors determined that its heterodimeric receptor is structurally related to the IL-10 receptor and therefore assigned IL-20 to the IL-10 subfamily within class II cytokines.1 Nevertheless, concurrently with its discovery, Blumberg et al have demonstrated that the biological activity of IL-20 in skin and its role in psoriasis is opposite to that of IL-10.2

In this issue of Arteriosclerosis, Thrombosis, and Vascular Biology, Chen et al show that IL-20 and its receptors are expressed in human and experimental atherosclerotic plaques. More importantly, the authors demonstrate that systemic delivery of IL-20 accelerates atherogenesis in the apolipoprotein E–knockout mouse model.3

Thus, as in the case of psoriasis, the role of IL-20 appears to be opposite to that of the structurally related IL-10 in atherosclerosis.4,5

Of note, at variance with the antiangiogenic action of IL-10,6 it has recently been described that IL-207 has both direct and indirect angiogenic effects. Such angiogenic potential has consequently been explored by the authors as an important putative proatherogenic mechanism. Indeed, plaque growth in the intimal space is inevitably accompanied by the development of an hypoxic condition within the atherosclerotic wall. As a consequence, hypoxia-induced proangiogenic factors are released and drive local neovascularization. The intraplaque neovessels are immature and hence prone to rupture. The subsequent intraplaque hemorrhage and accumulation of cholesterol from erythrocyte membranes in the necrotic core accelerates plaque growth and atherosclerotic complications.8,9

Therefore, the recent burst of enthusiasm and research focused around angiogenic strategies as therapeutic tools for the treatment of ischemic atherosclerotic diseases10 shall be carefully considered against the potential proatherogenic "side effects" of such approaches. Experimental studies have already shown that proangiogenic bone marrow–derived cells accelerate experimental atherosclerosis,11 whereas antiangiogenic treatment reduces disease extent.12 The present finding that IL-20 exerts proangiogenic and proatherogenic effects adds to the growing evidence for a deleterious role of systemic treatments aimed at promoting angiogenesis in atherosclerotic disease.

As the field of cytokine research progresses, a considerable number of cytokines (tumor necrosis factor [TNF]-{alpha}, IL-1, IL-2, IL-3, IL-6, IL-8, IL-12, IL-18, IFN-{gamma} ...) has already been identified as contributing to the building up of the atherosclerotic plaques.1 Although the proatherogenic role for most of them results from the accumulation of cellular and extracellular components in the arterial wall (Figure), the work by Chen et al indicates that the proangiogenic IL-20 might as well add another brick in the wall.


Figure 1
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Proatherogenic cytokines contribute to plaque growth through their effect on the accumulation of the cellular (smooth muscle cells [SMCs], leukocytes) and extracellular (matrix) moyeties. The novel proatherogenic cytokine IL-20 might exerts its proatherogenic action through the formation of neovessels.


*    Acknowledgments
 
Disclosures

None.


*    References
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*References
 

  1. Tedgui A, Mallat Z. Cytokines in atherosclerosis: pathogenic and regulatory pathways. Physiol Rev. 2006; 86: 515–581.[Abstract/Free Full Text]
  2. Blumberg H, Conklin D, Xu WF, Grossmann A, Brender T, Carollo S, Eagan M, Foster D, Haldeman BA, Hammond A, Haugen H, Jelinek L, Kelly JD, Madden K, Maurer MF, Parrish-Novak J, Prunkard D, Sexson S, Sprecher C, Waggie K, West J, Whitmore TE, Yao L, Kuechle MK, Dale BA, Chandrasekher YA. Interleukin 20: discovery, receptor identification, and role in epidermal function. Cell. 2001; 104: 9–19.[CrossRef][Medline] [Order article via Infotrieve]
  3. Chen WY, Cheng BC, Jiang MJ, Hsieh MY, Chang MS. IL-20 is expressed in atherosclerosis plaques and promotes atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2006; 26; 2090–2095.[Abstract/Free Full Text]
  4. Caligiuri G, Rudling M, Ollivier V, Jacob MP, Michel JB, Hansson GK, Nicoletti A. Interleukin-10 deficiency increases atherosclerosis, thrombosis, and low-density lipoproteins in apolipoprotein E knockout mice. Mol Med. 2003; 9: 10–17.[Medline] [Order article via Infotrieve]
  5. Mallat Z, Besnard S, Duriez M, Deleuze V, Emmanuel F, Bureau MF, Soubrier F, Esposito B, Duez H, Fievet C, Staels B, Duverger N, Scherman D, Tedgui A. Protective role of interleukin-10 in atherosclerosis. Circ Res. 1999; 85: e17–e24.[Abstract/Free Full Text]
  6. Silvestre JS, Mallat Z, Duriez M, Tamarat R, Bureau MF, Scherman D, Duverger N, Branellec D, Tedgui A, Levy BI. Antiangiogenic effect of interleukin-10 in ischemia-induced angiogenesis in mice hindlimb. Circ Res. 2000; 87: 448–452.[Abstract/Free Full Text]
  7. Hsieh MY, Chen WY, Jiang MJ, Cheng BC, Huang TY, Chang MS. Interleukin-20 promotes angiogenesis in a direct and indirect manner. Genes Immun. 2006; 7: 234–242.[CrossRef][Medline] [Order article via Infotrieve]
  8. Kolodgie FD, Gold HK, Burke AP, Fowler DR, Kruth HS, Weber DK, Farb A, Guerrero LJ, Hayase M, Kutys R, Narula J, Finn AV, Virmani R. Intraplaque hemorrhage and progression of coronary atheroma. N Engl J Med. 2003; 349: 2316–2325.[Abstract/Free Full Text]
  9. Virmani R, Kolodgie FD, Burke AP, Finn AV, Gold HK, Tulenko TN, Wrenn SP, Narula J. Atherosclerotic plaque progression and vulnerability to rupture: angiogenesis as a source of intraplaque hemorrhage. Arterioscler Thromb Vasc Biol. 2005; 25: 2054–2061.[Abstract/Free Full Text]
  10. Freedman SB, Isner JM. Therapeutic angiogenesis for coronary artery disease. Ann Intern Med. 2002; 136: 54–71.[Abstract/Free Full Text]
  11. Silvestre JS, Gojova A, Brun V, Potteaux S, Esposito B, Duriez M, Clergue M, Le Ricousse-Roussanne S, Barateau V, Merval R, Groux H, Tobelem G, Levy B, Tedgui A, Mallat Z. Transplantation of bone marrow-derived mononuclear cells in ischemic apolipoprotein E-knockout mice accelerates atherosclerosis without altering plaque composition. Circulation. 2003; 108: 2839–2842.[Abstract/Free Full Text]
  12. Moulton KS, Heller E, Konerding MA, Flynn E, Palinski W, Folkman J. Angiogenesis inhibitors endostatin or TNP-470 reduce intimal neovascularization and plaque growth in apolipoprotein E-deficient mice. Circulation. 1999; 99: 1726–1732.[Abstract/Free Full Text]

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IL-20 Is Expressed in Atherosclerosis Plaques and Promotes Atherosclerosis in Apolipoprotein E–Deficient Mice
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