This Article Full Text Full Text (PDF) Methods Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sartipy, P. Articles by Hurt-Camejo, E. Search for Related Content PubMed PubMed Citation Articles by Sartipy, P. Articles by Hurt-Camejo, E. Related Collections Other arteriosclerosis Other Vascular biology

(Circulation Research. 2000;86:707.)
© 2000 American Heart Association, Inc.

Clinical Research

Molecular Basis for the Association of Group IIA Phospholipase A₂ and Decorin in Human Atherosclerotic Lesions

Peter Sartipy, Berit Johansen, Kathrine Gåsvik, Eva Hurt-Camejo

From Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, Göteborg, Sweden (P.S., E.H.-C.), and the Department of Botany/UNIGEN Center for Molecular Biology, Norwegian University of Science and Technology, Trondheim, Norway (B.J., K.G.).

Correspondence to Peter Sartipy, Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, Göteborg 413 45, Sweden. E-mail peter.sartipy{at}wlab.wall.gu.se

Abstract—Group IIA secretory nonpancreatic phospholipase A₂ (snpPLA₂) is associated with collagen fibers in the extracellular matrix of human atherosclerotic plaques. Decorin, a small proteoglycan (PG) carrying chondroitin/dermatan sulfate glycosaminoglycans (GAGs), forms part of the collagen network in human arteries. To explore whether snpPLA₂ may be associated with collagen fibers via interaction with decorin, we performed (1) immunohistochemistry to compare the relative in vivo localization of snpPLA₂ and decorin in human atherosclerotic tissue and (2) in vitro experiments to study the interaction between snpPLA₂ and decorin. In atherosclerotic lesions, decorin was detected within the snpPLA₂-positive part of the intima close to the media. Electrophoretic mobility shift assay showed that snpPLA₂ binds to decorin synthesized by human fibroblasts. Native and GAG-depleted decorin enhanced the association of snpPLA₂ to collagen types I and VI in a solid-phase binding assay. Furthermore, snpPLA₂ bound efficiently to a recombinant decorin core protein fragment B/E (Asp45-Lys359). This binding was competed with soluble decorin and inhibited at NaCl concentrations >150 mmol/L. The decorin core protein fragment B/E competed better than dermatan sulfate for binding of snpPLA₂ to decorin-coated microtiter wells. The enzymatic activity of snpPLA₂ increased 2- to 3-fold in the presence of decorin or GAG-depleted decorin. The results show that snpPLA₂ binds preferentially to the decorin protein core rather than to the GAG chain and that this interaction enhances snpPLA₂ activity. As a consequence, this active extracellular enzyme may contribute to the pathogenesis of atherosclerosis by modifying lipoproteins and releasing inflammatory lipid mediators at places of lipoprotein retention in the arterial wall.

Key Words: atherosclerosis • decorin • group IIA phospholipase A₂

This article has been cited by other articles:

				H. Sato, R. Kato, Y. Isogai, G.-i. Saka, M. Ohtsuki, Y. Taketomi, K. Yamamoto, K. Tsutsumi, J. Yamada, S. Masuda, et al. Analyses of Group III Secreted Phospholipase A2 Transgenic Mice Reveal Potential Participation of This Enzyme in Plasma Lipoprotein Modification, Macrophage Foam Cell Formation, and Atherosclerosis J. Biol. Chem., November 28, 2008; 283(48): 33483 - 33497. [Abstract] [Full Text] [PDF]

				J. Saegusa, N. Akakura, C.-Y. Wu, C. Hoogland, Z. Ma, K. S. Lam, F.-T. Liu, Y. K. Takada, and Y. Takada Pro-inflammatory Secretory Phospholipase A2 Type IIA Binds to Integrins {alpha}v{beta}3 and {alpha}4{beta}1 and Induces Proliferation of Monocytic Cells in an Integrin-dependent Manner J. Biol. Chem., September 19, 2008; 283(38): 26107 - 26115. [Abstract] [Full Text] [PDF]

				B. Rosengren, H. Peilot, M. Umaerus, A.-C. Jonsson-Rylander, L. Mattsson-Hulten, C. Hallberg, P. Cronet, M. Rodriguez-Lee, and E. Hurt-Camejo Secretory Phospholipase A2 Group V: Lesion Distribution, Activation by Arterial Proteoglycans, and Induction in Aorta by a Western Diet Arterioscler Thromb Vasc Biol, July 1, 2006; 26(7): 1579 - 1585. [Abstract] [Full Text] [PDF]

				A. Jaulmes, B. Janvier, M. Andreani, and M. Raymondjean Autocrine and Paracrine Transcriptional Regulation of Type IIA Secretory Phospholipase A2 Gene in Vascular Smooth Muscle Cells Arterioscler Thromb Vasc Biol, June 1, 2005; 25(6): 1161 - 1167. [Abstract] [Full Text] [PDF]

				S. A. I. Ghesquiere, M. J. J. Gijbels, M. Anthonsen, P. J. J. van Gorp, I. van der Made, B. Johansen, M. H. Hofker, and M. P. J. de Winther Macrophage-specific overexpression of group IIa sPLA2 increases atherosclerosis and enhances collagen deposition J. Lipid Res., February 1, 2005; 46(2): 201 - 210. [Abstract] [Full Text] [PDF]

				E. Boilard, S. G. Bourgoin, C. Bernatchez, and M. E. Surette Identification of an autoantigen on the surface of apoptotic human T cells as a new protein interacting with inflammatory group IIA phospholipase A2 Blood, October 15, 2003; 102(8): 2901 - 2909. [Abstract] [Full Text] [PDF]

				B. OSTERUD and E. BJORKLID Role of Monocytes in Atherogenesis Physiol Rev, October 1, 2003; 83(4): 1069 - 1112. [Abstract] [Full Text] [PDF]

				S. Akiba, Y. Yoneda, S. Ohno, M. Nemoto, and T. Sato Oxidized LDL activates phospholipase A2 to supply fatty acids required for cholesterol esterification J. Lipid Res., September 1, 2003; 44(9): 1676 - 1685. [Abstract] [Full Text] [PDF]

				S. Beck, G. Lambeau, K. Scholz-Pedretti, M. H. Gelb, M. J. W. Janssen, S. H. Edwards, D. C. Wilton, J. Pfeilschifter, and M. Kaszkin Potentiation of Tumor Necrosis Factor {alpha}-induced Secreted Phospholipase A2 (sPLA2)-IIA Expression in Mesangial Cells by an Autocrine Loop Involving sPLA2 and Peroxisome Proliferator-activated Receptor {alpha} Activation J. Biol. Chem., August 8, 2003; 278(32): 29799 - 29812. [Abstract] [Full Text] [PDF]

				K. Hanasaki, K. Yamada, S. Yamamoto, Y. Ishimoto, A. Saiga, T. Ono, M. Ikeda, M. Notoya, S. Kamitani, and H. Arita Potent Modification of Low Density Lipoprotein by Group X Secretory Phospholipase A2 Is Linked to Macrophage Foam Cell Formation J. Biol. Chem., August 2, 2002; 277(32): 29116 - 29124. [Abstract] [Full Text] [PDF]

				E. Hurt-Camejo, G. Camejo, H. Peilot, K. Oorni, and P. Kovanen Phospholipase A2 in Vascular Disease Circ. Res., August 17, 2001; 89(4): 298 - 304. [Abstract] [Full Text] [PDF]

				L. Nelimarkka, H. Salminen, T. Kuopio, S. Nikkari, T. Ekfors, J. Laine, L. Pelliniemi, and H. Jarvelainen Decorin Is Produced by Capillary Endothelial Cells in Inflammation-Associated Angiogenesis Am. J. Pathol., February 1, 2001; 158(2): 345 - 353. [Abstract] [Full Text] [PDF]

				K. Öörni, M. O. Pentikäinen, M. Ala-Korpela, and P. T. Kovanen Aggregation, fusion, and vesicle formation of modified low density lipoprotein particles: molecular mechanisms and effects on matrix interactions J. Lipid Res., November 1, 2000; 41(11): 1703 - 1714. [Abstract] [Full Text]

				P. T. Kovanen and M. O. Pentikainen Secretory Group II Phospholipase A2 : A Newly Recognized Acute-Phase Reactant With a Role in Atherogenesis Circ. Res., March 31, 2000; 86(6): 610 - 612. [Full Text] [PDF]

				M. Murakami, R. S. Koduri, A. Enomoto, S. Shimbara, M. Seki, K. Yoshihara, A. Singer, E. Valentin, F. Ghomashchi, G. Lambeau, et al. Distinct Arachidonate-releasing Functions of Mammalian Secreted Phospholipase A2s in Human Embryonic Kidney 293 and Rat Mastocytoma RBL-2H3 Cells through Heparan Sulfate Shuttling and External Plasma Membrane Mechanisms J. Biol. Chem., March 23, 2001; 276(13): 10083 - 10096. [Abstract] [Full Text] [PDF]

				M. Hernandez, L. Fuentes, F. J. Fernandez Aviles, M. S. Crespo, and M. L. Nieto Secretory Phospholipase A2 Elicits Proinflammatory Changes and Upregulates the Surface Expression of Fas Ligand in Monocytic Cells: Potential Relevance for Atherogenesis Circ. Res., January 11, 2002; 90(1): 38 - 45. [Abstract] [Full Text] [PDF]